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PubMed - Insulinoma (100 unread)

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Anaesthesia management of a patient with non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) - A case study

Fetched: December 5th, 2023, 5:02am GMT by Bhanupreet Kaur

Indian J Anaesth. 2023 Oct;67(10):944-945. doi: 10.4103/ija.ija_1017_22. Epub 2023 Oct 16.

NO ABSTRACT

PMID:38044917 | PMC:PMC10691616 | DOI:10.4103/ija.ija_1017_22

Permalink for 'Immunohistochemical and in situ hybridization analyses of glucose transporter 2 in pancreatic neuroendocrine tumors: Possible glucose transporter 2 association with neoplastic insulin production'

Immunohistochemical and in situ hybridization analyses of glucose transporter 2 in pancreatic neuroendocrine tumors: Possible glucose transporter 2 association with neoplastic insulin production

Fetched: December 4th, 2023, 5:01am GMT by Hirofumi Watanabe

Pathol Res Pract. 2023 Nov 24;253:154966. doi: 10.1016/j.prp.2023.154966. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms. Additionally, glucose transporter 2 (GLUT2) is associated with insulin production and is essential for glucose transport to normal pancreatic β-cells. Neoplastic cell GLUT2 expression may also influence insulin production by using this transporter. GLUT2 expression and its clinical significance remain unclear in PanNETs. This study aimed to provide GLUT2 expression profiles and evidence of correlation with insulin in PanNETs.

METHODS: Clinical data were retrieved from 113 surgically resected paraffin-embedded PanNET tissue samples fixed with 10% formalin. PanNETs are categorized as insulinoma, non-functional (NF)-PanNET, or PanNET-not otherwise specified (NOS). A GLUT2 score was used to evaluate cytoplasmic GLUT2 immunoreactivity. The immunoreactive score (IRS) was used to determine membranous GLUT2, cytoplasmic insulin, and proinsulin immunoreactivities. A commercially available in situ hybridization (ISH) kit detected human SLC2A2 (GLUT2) mRNA on tissues in all seven positive- and 20 negative-GLUT2 IRS cases.

RESULTS: GLUT2 and IRSs significantly differed among insulinoma, NF-PanNET, and PanNET-NOS. Insulinomas exhibited significantly higher GLUT2 scores and IRSs than did NF-PanNETs. GLUT2 IRS positive cases demonstrated significantly higher insulin and proinsulin IRSs than did negative cases. Additionally, GLUT2 ISH-positive cases demonstrated positive GLUT2 scores and IRSs, with significantly higher GLUT2 IRSs than did negative cases. PanNET histological grade categories did not significantly affect GLUT2 scores and IRSs.

CONCLUSION: The first evidence of a correlation between GLUT2 expressions and insulin in PanNETs is shown in this study.

PMID:38043192 | DOI:10.1016/j.prp.2023.154966

Analysis of Hypoglycemic Drugs by Liquid Chromatography-Tandem Mass Spectrometry

Fetched: December 1st, 2023, 5:02am GMT by Paul J Jannetto

Methods Mol Biol. 2024;2737:297-306. doi: 10.1007/978-1-0716-3541-4_27.

ABSTRACT

A rapid and simple method to measure oral hypoglycemic agents is essential in the evaluation of a patient with spontaneous hypoglycemia. As a result, a robust high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the qualitative detection of first-generation sulfonylureas (e.g., chlorpropamide, tolazamide, and tolbutamide), second-generation sulfonylureas (e.g., glimepiride, glipizide, and glyburide), meglitinides (e.g., repaglinide, nateglinide), and thiazolidinediones (e.g., rosiglitazone and pioglitazone). HPLC involved a C8 column and MS/MS was used in electrospray ionization (ESI) positive mode. Identification of all compounds was made using various multiple-reaction monitoring (MRMs). Isotopic labeled chlorpropamide-d4, glimepiride-d5, glyburide-d11, nateglinide-d5, repaglinide-ethyl-d5, rosiglitazone-d3, and zomepirac were used as the internal standards. The cutoffs for each drug were as follows: chlorpropamide 100 ng/mL, tolazamide 50 ng/mL, tolbutamide 20 ng/mL, glimepiride 20 ng/mL, glipizide 5 ng/mL, glyburide 5 ng/mL, repaglinide 5 ng/mL, rosiglitazone 20 ng/mL, pioglitazone 20 ng/mL, and nateglinide 5 ng/mL.

PMID:38036831 | DOI:10.1007/978-1-0716-3541-4_27

Permalink for 'Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)/Nesidioblastosis as the underlying cause of recurrent hypoglycemia in a diabetic adult'

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)/Nesidioblastosis as the underlying cause of recurrent hypoglycemia in a diabetic adult

Fetched: December 1st, 2023, 5:02am GMT by Samikshya Thapa

Autops Case Rep. 2023 Oct 27;13:e2023451. doi: 10.4322/acr.2023.451. eCollection 2023.

ABSTRACT

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), without previous bariatric surgery, is a rare form of hypoglycemia in adult patients and is associated with nesidioblastosis. Adult-onset nesidioblastosis in diabetic patients is rare and histologically identical to "non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)". Nesidioblastosis is rare in adults and clinically and biochemically mimics Insulinoma. In the literature, there have only been four cases of adult nesidioblastosis that followed diabetes mellitus. We report a case of nesidioblastosis in a 36-year-old diabetic female presenting with dizziness, sweating, and palpitations for three years. Selective non-invasive techniques failed to detect a tumor. Based on the pursuit of an insulinoma, a distal pancreatectomy specimen was received at our laboratory, and a diagnosis of nesidioblastosis was made. She is currently on follow-up with a favorable outcome. The definitive diagnosis of nesidioblastosis is made on a histological basis. The preferred form of treatment is pancreatic surgical resection. Nesidioblastosis should be taken into consideration in cases where diabetes transforms into hyperinsulinemic hypoglycemia.

PMID:38034512 | PMC:PMC10687782 | DOI:10.4322/acr.2023.451

Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion

Fetched: December 1st, 2023, 5:02am GMT by Abigael Cheruiyot

J Clin Invest. 2023 Nov 30:e173280. doi: 10.1172/JCI173280. Online ahead of print.

ABSTRACT

Pancreatic beta-cells are specialized for coupling glucose metabolism to insulin peptide production and secretion. Acute glucose exposure robustly and coordinately increases translation of proinsulin and proteins required for secretion of mature insulin peptide. By contrast, chronically elevated glucose levels that occur during diabetes impair beta-cell insulin secretion and have been shown experimentally to suppress insulin translation. Whether translation of other genes critical for insulin secretion are similarly downregulated by chronic high glucose is unknown. Here, we used high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells to elucidate the genome-wide impact of sustained high glucose on beta-cell mRNA translation. Prior to induction of ER stress or suppression of global translation, sustained high glucose suppressed glucose-stimulated insulin secretion and downregulated translation of not only insulin, but also of mRNAs related to insulin secretory granule formation, exocytosis, and metabolism-coupled insulin secretion. Translation of these mRNAs was also downregulated in primary rat and human islets following ex-vivo incubation with sustained high glucose and in an in vivo model of chronic mild hyperglycemia. Furthermore, translational downregulation decreased cellular abundance of these proteins. Our study uncovered a translational regulatory circuit during beta-cell glucose toxicity that impairs expression of proteins with critical roles in beta-cell function.

PMID:38032734 | DOI:10.1172/JCI173280

Neuroendocrine neoplasms in the breast oncology field: dilemmas of nature and morphology

Fetched: December 1st, 2023, 5:02am GMT by Tomonori Kawasaki

Front Endocrinol (Lausanne). 2023 Nov 1;14:1216424. doi: 10.3389/fendo.2023.1216424. eCollection 2023.

NO ABSTRACT

PMID:38027104 | PMC:PMC10646302 | DOI:10.3389/fendo.2023.1216424

A Case of Insulin Autoimmune Syndrome Accompanied With Systemic Joint Pain: A Case Report

Fetched: December 1st, 2023, 5:02am GMT by Yuta Horinishi

Cureus. 2023 Oct 16;15(10):e47140. doi: 10.7759/cureus.47140. eCollection 2023 Oct.

ABSTRACT

Insulin autoimmune syndrome (IAS) is a rare disorder characterised by autoantibodies against endogenous insulin that cause spontaneous hypoglycemic episodes. Here, we present the case of a 66-year-old male with polyarticular pain and dizziness that was initially suspected to be an insulinoma. However, further testing confirmed the presence of IAS. The patient's joint pain fluctuated but improved with the control of blood glucose levels. Although the direct relationship between IAS and joint pain is not well established, individuals with a single autoimmune disorder may develop concurrent autoimmune conditions. Joint pain is prevalent in patients with autoimmune diseases. Although hypoglycemia may cause muscle cramps due to stress responses, direct musculoskeletal damage is uncommon. This case underscores the importance of differential diagnosis, particularly in differentiating between pancreatic cancer and the benign proliferation of pancreatic B cells. Elevated levels of insulin autoantibodies confirm IAS, whereas pancreatic cancer may manifest various symptoms and elevated cancer antigens (CA) 19-9. General physicians should comprehensively investigate hypoglycemia cases, particularly those associated with pancreatic enlargement, and continually monitor for potential malignancies.

PMID:38021632 | PMC:PMC10650969 | DOI:10.7759/cureus.47140

Proinsulin: physiology, measurement, and interest in clinical biology

Fetched: December 1st, 2023, 5:02am GMT by Katia Carvalho Alves

Ann Biol Clin (Paris). 2023 Nov 29;81(5). doi: 10.1684/abc.2023.1838. Online ahead of print.

ABSTRACT

The proinsulin molecule results from the cleavage of pre-pro-insulin, produced in pancreatic beta cells. Its subsequent -cleavage allows the release of insulin, the key hormone of glycemia regulation and C-peptide in equimolar proportions. During fasting trial, insulinoma diagnosis relies on inadequately high insulin and C-peptide serum levels concomitant with an hypoglycemia. In this context, proinsulin assay can be interesting in the cases of discrepancy between the two parameters. In diabetes, endoplasmic reticulum stress and beta cells inflammation, lead to the secretion of misfolded proinsulin molecules. Thus, in type 2 diabetes, proinsulin/insulin ratio increases with the degree of insulin resistance. In type 1 diabetes, proinsulin/C-peptide ratio could predict the onset of diabetes in relatives. In our practice, serum pro-insulin determined using an Elisa immunoassay (Millipore®) during fasting trial can be complementary to C-peptide and insulin assays in relation to glycemia to label an hypoglycemia. In case of glucose intolerance and diabetes, proinsulin could thus be measured.

PMID:38018823 | DOI:10.1684/abc.2023.1838

Robotic Enucleation of Pancreatic Head Insulinomas in Close Proximity to the Pancreatic Duct

Fetched: November 29th, 2023, 5:02am GMT by Patricio M Polanco

Ann Surg Oncol. 2023 Nov 28. doi: 10.1245/s10434-023-14627-5. Online ahead of print.

ABSTRACT

BACKGROUND: Insulinomas are rare pancreatic neuroendocrine tumors for which the main curative treatment is surgical resection. Enucleation is preferred over pancreatoduodenectomy to minimize morbidity and function loss.¹ Robotic-assisted surgery offers improved versatility and less blood loss than laparoscopic surgery for pancreatic enucleation.^2-4 Our video describes the technique for robotic enucleation of pancreatic head insulinomas in close proximity to the pancreatic duct.

PATIENTS AND METHODS: The video describes the presentation, diagnostic imaging, and technical aspects of the surgical approach in two patients with pancreatic head insulinomas that underwent robotic enucleation.

RESULTS: Case one was a 76-year-old woman who experienced syncope for 2 months. Case two was a 61-year-old man, previously treated for renal cancer, who had documented hypoglycemic symptoms. Computed tomography (CT) scan and magnetic resonance imaging (MRI) identified a 1.5 cm and 1.2 cm pancreatic head mass, respectively. Both patients presented with low glucose levels, and elevated C-peptide and proinsulin. In both cases, endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic duct stent placement were performed the same day of surgery for intraoperative identification and preservation of the duct. Robotic enucleation of the masses was performed, and an ultrasound was used to identify the masses and relation with main pancreatic duct. Pathology revealed a well-differentiated neuroendocrine tumor in both cases. The patient's postoperative course was uneventful, and they were discharged on day 5. Successful resolution of hypoglycemic events occurred in both patients.

CONCLUSION: Robotic enucleation is a safe and feasible option for treating pancreatic head tumors in challenging locations. Intraoperative ultrasound is an essential tool for the successful robotic enucleation of pancreatic head tumors.

PMID:38017126 | DOI:10.1245/s10434-023-14627-5

Permalink for 'Evaluation of plasma cortisol during fasting test in patients with endogenous hyperinsulinemic hypoglycemia. Fifteen years experience'

Evaluation of plasma cortisol during fasting test in patients with endogenous hyperinsulinemic hypoglycemia. Fifteen years experience

Fetched: November 29th, 2023, 5:02am GMT by María Eugenia Gullace

Endocrinol Diabetes Nutr (Engl Ed). 2023 Nov 27:S2530-0180(23)00171-3. doi: 10.1016/j.endien.2023.11.008. Online ahead of print.

ABSTRACT

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare clinical condition. The aim of this study was to evaluate baseline plasma cortisol concentration and its concentration during hypoglycemic crisis in fasting tests (FT) performed in our center. Secondarily, the aim was to establish the relationship between baseline cortisol and the time of evolution of EHH.

MATERIAL AND METHODS: A retrospective, observational, descriptive study was carried out which included patients with hypoglycemic disorder with positive FT.

RESULTS: Of a total of 21 patients, 16 presented insulinoma, 1 nesidioblastosis, 2 malignant insulinoma and 2 EHH without pathological diagnosis. The time from the onset of symptoms to diagnosis was 2 years (Q1=1.5-Q2=5.5). The comparison between median baseline cortisol (BC)=11.8 mcg/dl (nmol/L 340.68) (Q1=9-Q3=14.1) and median cortisol during hypoglycemic episode (HC)=11.6 mcg/dl (nmol/L: 303.44) (Q1=7.8-Q3=16.1) showed no differences (Z=-0.08; P>.05). When correlating BC with HC, no significant relationship was observed (r=0.16; P>.05). When correlating the glycemic value in the crisis and the HC, a slight negative trend was found (r=-0.53; P=.01). In addition, we found that recurrent hypoglycemic disorder is associated with lower baseline cortisol values the longer the time of its evolution.

CONCLUSION: We confirmed that cortisol values remain low during hypoglycemic episodes, reinforcing the hypothesis of lack of response of this counterregulatory hormone in cases of recurrent hypoglycemia.

PMID:38016856 | DOI:10.1016/j.endien.2023.11.008

A review on nondiabetic hypoglycemia from various causes: Case series report

Fetched: November 29th, 2023, 5:02am GMT by Lulu Gan

Medicine (Baltimore). 2023 Nov 24;102(47):e36273. doi: 10.1097/MD.0000000000036273.

ABSTRACT

RATIONALE: Hypoglycemia is common in patients with glucose regulation disorders and related diabetic treatments but is rare in nondiabetic patients. Severe hypoglycemia can cause harm to patients' cognition, consciousness, central nervous system, cardiovascular and cerebrovascular system, and even death. However, the most fundamental way to control hypoglycemia is to identify the cause and deal with the primary disease. This article introduces 3 cases of nondiabetic hypoglycemia with different causes, aiming to improve our understanding of nondiabetic hypoglycemia and improve the ability of early diagnosis and differential diagnosis.

PATIENT CONCERNS: Case 1 is a 19-year-old female with a history of recurrent coma, and magnetic resonance imaging and endoscopic ultrasound of the pancreas suggest insulinoma. Case 2 is a 74-year-old male with a history of viral hepatitis, and computerized tomography shows multiple nodules in the liver, which is diagnosed as liver cancer. Case 3 is a 39-year-old female with a history of taking methimazole, who tested positive for insulin antibodies, and was diagnosed with insulin autoimmune syndrome.

DIAGNOSIS: All 3 patients were diagnosed with nondiabetic hypoglycemia, but the causes varied, and included insulinoma, non-islet cell tumor-induced hypoglycemia, and insulin autoimmune syndrome.

INTERVENTIONS: Case 1 underwent pancreatic tail resection; case 2 refused anti-tumor treatment and received glucose injections for palliative treatment only; and case 3 stopped taking methimazole.

OUTCOMES: After surgery, the blood sugar in case 1 returned to normal, and the blood sugar in case 2 was maintained at about 6.0 mmol/L. The symptoms of hypoglycemia gradually improved in case 3 after stopping the medication.

LESSONS: Non-diabetic hypoglycemia requires further examination to clarify the cause, and the correct differential diagnosis can provide timely and effective treatment, improving the patient's prognosis.

PMID:38013348 | PMC:PMC10681503 | DOI:10.1097/MD.0000000000036273

Human Pancreatic Islets React to Glucolipotoxicity by Secreting Pyruvate and Citrate

Fetched: November 26th, 2023, 5:02am GMT by Johan Perrier

Nutrients. 2023 Nov 15;15(22):4791. doi: 10.3390/nu15224791.

ABSTRACT

Progressive decline in pancreatic beta-cell function is central to the pathogenesis of type 2 diabetes (T2D). Here, we explore the relationship between the beta cell and its nutritional environment, asking how an excess of energy substrate leads to altered energy production and subsequent insulin secretion. Alterations in intracellular metabolic homeostasis are key markers of islets with T2D, but changes in cellular metabolite exchanges with their environment remain unknown. We answered this question using nuclear magnetic resonance-based quantitative metabolomics and evaluated the consumption or secretion of 31 extracellular metabolites from healthy and T2D human islets. Islets were also cultured under high levels of glucose and/or palmitate to induce gluco-, lipo-, and glucolipotoxicity. Biochemical analyses revealed drastic alterations in the pyruvate and citrate pathways, which appear to be associated with mitochondrial oxoglutarate dehydrogenase (OGDH) downregulation. We repeated these manipulations on the rat insulinoma-derived beta-pancreatic cell line (INS-1E). Our results highlight an OGDH downregulation with a clear effect on the pyruvate and citrate pathways. However, citrate is directed to lipogenesis in the INS-1E cells instead of being secreted as in human islets. Our results demonstrate the ability of metabolomic approaches performed on culture media to easily discriminate T2D from healthy and functional islets.

PMID:38004183 | PMC:PMC10674605 | DOI:10.3390/nu15224791

Permalink for 'Nrf2 inhibition regulates intracellular lipid accumulation in mouse insulinoma cells and improves insulin secretory function'

Nrf2 inhibition regulates intracellular lipid accumulation in mouse insulinoma cells and improves insulin secretory function

Fetched: November 26th, 2023, 5:02am GMT by Alpana Mukhuty

Mol Cell Endocrinol. 2023 Nov 23;581:112112. doi: 10.1016/j.mce.2023.112112. Online ahead of print.

ABSTRACT

High amount of fat in the pancreas is linked to poor functioning of β-cells and raises the risk of type 2 diabetes. Here we report the putative role of a circulatory glycoprotein Fetuin-A, a known obesity marker, in promoting lipid accumulation in β-cells and its association with Fatty acid translocase/CD36 for lipid storage culminate in β-cell dysfunction. Additionally, this work reveals regulation of CD36 via Nrf2, a key regulator of oxidative stress, and reduction of lipid accumulation by suppression of Nrf2 that restores β-cell function. Palmitate (0.50 mM) and Fetuin-A (100 μg/mL) exposure showed high levels of intracellular lipid in MIN6 (mouse insulinoma cells) with a concomitant decrease in insulin secretion. This also increased the expression of important lipogenic factors, like CD36, PGC1α, PPARγ, and SREBP1. Flow cytometry analysis of CD36 membrane localization has been corroborated with an increased accumulation of lipids as indicated by Oil-Red-O staining. Immunoblotting and immunofluorescence of Nrf2 indicated its high expression in palmitate-fetuin-A incubation and translocation in the nucleus. Suppression of Nrf2 by siRNA showed a reduced expression of lipogenic genes, ablation of lipid droplets, decrease in the number of apoptotic cells, and restoration of insulin secretion with a corresponding increase of Pdx1, BETA2, and Ins1 gene expression. Our study thus suggested an important aspect of lipid accumulation in the pancreatic β-cells contributing to β-cell dysfunction and demonstrated the role of Fetuin-A in CD36 expression, with a possible way of restoring β-cell function by targeting Nrf2.

PMID:38000461 | DOI:10.1016/j.mce.2023.112112

Insm1 regulates mTEC development and immune tolerance

Fetched: November 23rd, 2023, 5:03am GMT by Weihua Tao

Cell Mol Immunol. 2023 Dec;20(12):1472-1486. doi: 10.1038/s41423-023-01102-0. Epub 2023 Nov 21.

ABSTRACT

The expression of self-antigens in medullary thymic epithelial cells (mTECs) is essential for the establishment of immune tolerance, but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood. Here, we show that Insm1, a zinc finger protein with known functions in neuroendocrine and neuronal cells, is broadly coexpressed with an autoimmune regulator (Aire) in mTECs. Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells. Mutation of Insm1 in mice downregulated Aire expression, dysregulated the gene expression program of mTECs, and altered mTEC subpopulations and the expression of tissue-restricted antigens. Consistent with these findings, loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues. We found that Insm1 regulates gene expression in mTECs by binding to chromatin. Interestingly, the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions. Together, our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.

PMID:37990032 | PMC:PMC10687002 | DOI:10.1038/s41423-023-01102-0

Permalink for 'Combined Astragalus, vitamin C, and vitamin E alleviate DEHP-induced oxidative stress and the decreased of insulin synthesis and secretion in INS-1 cells'

Combined Astragalus, vitamin C, and vitamin E alleviate DEHP-induced oxidative stress and the decreased of insulin synthesis and secretion in INS-1 cells

Fetched: November 22nd, 2023, 5:02am GMT by Long Zhao

Ecotoxicol Environ Saf. 2023 Dec;268:115675. doi: 10.1016/j.ecoenv.2023.115675. Epub 2023 Nov 18.

ABSTRACT

Di-(2-ethylhexyl)-phthalate (DEHP), a common Phthalic acid ester (PAEs), has been reported to be associated with diabetes mellitus, yet the underlying mechanisms remain unknown. Combined nutrient interventions have been shown to alleviate the diabetic toxicity of DEHP. However, the effects and mechanisms of the combined intervention of Astragalus and vitamins (C and E) are currently unknown. In this study, we investigated the potential mechanisms of DEHP-induced diabetes mellitus through transcriptome analysis and vitro experiments using rat insulinoma cells (INS-1 cells). Furthermore, we explored the protection of the combined Astragalus, vitamin C, and vitamin E on DEHP-induced diabetes mellitus through these mechanisms. INS-1 cells in the logarithmic growth period were exposed to 125 umol/L DEHP followed by high-throughput sequencing analysis. The cell proliferation inhibition rate was determined using MTT assay for each group, and the cell apoptosis rate and intracellular ROS level were measured using flow cytometer. Finally, insulin levels and markers of oxidative stress were detected using ELISA kits in different groups. A total of 372 differentially expressed genes were found between the 125 umol/L DEHP and control groups, subsequent functional enrichment analyses indicated that DEHP induced oxidative stress and disturbed insulin levels. In INS-1 cells, the rate of cell proliferation inhibition, apoptosis, and the degree of oxidative stress increased concentration-dependently with increasing DEHP concentrations, while antioxidant intervention could reverse these changes. Insulin synthesis and secretion decreased after 240 μmol/L DEHP exposure stimulated by 25 mM glucose in INS-1 cells, also could antioxidant intervention alleviate these reductions. Based on these results, the underlying mechanism of DEHP impairing the function of INS-1 cells might be through apoptosis pathways induced by oxidative stress and direct reduction of insulin levels (both synthesis and secretion), while the optimal combination of Astragalus and vitamins (C and E) could exert an alleviating effect.

PMID:37984288 | DOI:10.1016/j.ecoenv.2023.115675

Permalink for 'Impact of Early Diagnostic and Therapeutic Interventions and Clinical Course in Children and Adolescents with Multiple Endocrine Neoplasia Types 1 and 2'

Impact of Early Diagnostic and Therapeutic Interventions and Clinical Course in Children and Adolescents with Multiple Endocrine Neoplasia Types 1 and 2

Fetched: November 19th, 2023, 5:01am GMT by Ja Hye Kim

Exp Clin Endocrinol Diabetes. 2023 Nov 16. doi: 10.1055/a-2212-7536. Online ahead of print.

ABSTRACT

OBJECTIVE: Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN.

METHODS: This study included 8 patients from 7 unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B.

RESULTS: Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11 ± 2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0 ± 2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age.

CONCLUSION: This study described the relatively long clinical course of pediatric MEN with mean follow-up duration of 7.5 ± 3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course.

PMID:37973156 | DOI:10.1055/a-2212-7536

Characterisation of transgenic pigs expressing a human T cell-depleting anti-CD2 monoclonal antibody

Fetched: November 15th, 2023, 5:03am GMT by Evelyn J Salvaris

Xenotransplantation. 2023 Nov 13:e12836. doi: 10.1111/xen.12836. Online ahead of print.

ABSTRACT

BACKGROUND: Pig islet xenotransplantation is a potential treatment for type 1 diabetes. We have shown that maintenance immunosuppression is required to protect genetically modified (GM) porcine islet xenografts from T cell-mediated rejection in baboons. Local expression of a depleting anti-CD2 monoclonal antibody (mAb) by the xenograft may provide an alternative solution. We have previously reported the generation of GGTA1 knock-in transgenic pigs expressing the chimeric anti-CD2 mAb diliximab under an MHC class I promoter (MHCIP). In this study, we generated GGTA1 knock-in pigs in which MHCIP was replaced by the β-cell-specific porcine insulin promoter (PIP), and compared the pattern of diliximab expression in the two lines.

METHODS: A PIP-diliximab knock-in construct was prepared and validated by transfection of NIT-1 mouse insulinoma cells. The construct was knocked into GGTA1 in wild type (WT) porcine fetal fibroblasts using CRISPR, and knock-in cells were used to generate pigs by somatic cell nuclear transfer (SCNT). Expression of the transgene in MHCIP-diliximab and PIP-diliximab knock-in pigs was characterised at the mRNA and protein levels using RT-qPCR, flow cytometry, ELISA and immunohistochemistry. Islets from MHCIP-diliximab and control GGTA1 KO neonatal pigs were transplanted under the kidney capsule of streptozotocin-diabetic SCID mice.

RESULTS: NIT-1 cells stably transfected with the PIP-diliximab knock-in construct secreted diliximab into the culture supernatant, confirming correct expression and processing of the mAb in β cells. PIP-diliximab knock-in pigs showed a precise integration of the transgene within GGTA1. Diliximab mRNA was detected in all tissues tested (spleen, kidney, heart, liver, lung, pancreas) in MHCIP-diliximab pigs, but was not detectable in PIP-diliximab pigs. Likewise, diliximab was present in the serum of MHCIP-diliximab pigs, at a mean concentration of 1.8 μg/mL, but was not detected in PIP-diliximab pig serum. An immunohistochemical survey revealed staining for diliximab in all organs of MHCIP-diliximab pigs but not of PIP-diliximab pigs. Whole genome sequencing (WGS) of a PIP-diliximab pig identified a missense mutation in the coding region for the dixilimab light chain. This mutation was also found to be present in the fibroblast knock-in clone used to generate the PIP-diliximab pigs. Islet xenografts from neonatal MHCIP-diliximab pigs restored normoglycemia in diabetic immunodeficient mice, indicating no overt effect of the transgene on islet function, and demonstrated expression of diliximab in situ.

CONCLUSION: Diliximab was widely expressed in MHCIP-diliximab pigs, including in islets, consistent with the endogenous expression pattern of MHC class I. Further investigation is required to determine whether the level of expression in islets from the MHCIP-diliximab pigs is sufficient to prevent T cell-mediated islet xenograft rejection. The unexpected absence of diliximab expression in the islets of PIP-diliximab pigs was probably due to a mutation in the transgene arising during the generation of the knock-in cells used for SCNT.

PMID:37961013 | DOI:10.1111/xen.12836

The Broad Spectrum of Paediatric Pancreatic Disease: A Single-center 26-years Retrospective Review

Fetched: November 14th, 2023, 5:02am GMT by Amr Alnagar

J Pediatr Surg. 2023 Oct 21:S0022-3468(23)00645-0. doi: 10.1016/j.jpedsurg.2023.10.035. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric pancreatic pathology and its management is rarely described. We present our experience.

METHODS: A retrospective case-note review of all patients with pancreatic disease from 1995 to 2021 was completed. Data are quoted as median (range).

RESULTS: Two hundred and twelve patients were identified with 75.9% presenting with pancreatitis. Referrals for pancreatitis increased during the study period and affected a wide age range (2 months-15.6 years). Acute pancreatitis (n = 118) (age 10.6 (0.18-16.3) years). The most common causes were idiopathic (n = 60, 50.8%) and biliary (n = 28, 23.8%). About 10% required treatment for complications or underlying biliary causes. Recurrent pancreatitis (n = 14) (11.6 (0.3-14.3) years). The most common cause was hereditary pancreatitis (n = 6, 42.9%). One patient required endoscopic drainage of pseudocyst. Chronic pancreatitis (n = 29) (16 (0.38-15.5) years). The underlying diagnosis was idiopathic (n = 14, 48.4%) or hereditary pancreatitis (n = 10, 34.5%). 13 patients required active management, including pancreaticojejunostomies (n = 5). Blunt Trauma (n = 34) was managed conservatively in 24 (70.5%). 6 patients required open surgery, but 4 were managed by either endoscopy or interventional radiology. Pancreatic tumours (n = 13) presented at 11.2 (2.3-16) years. Pathology included pancreaticoblastomas (n = 3), solid pseudopapillary tumours (n = 3), neuroendocrine tumours (n = 2), acinar cell cystadenoma (n = 1), intraductal papillary mucinous neoplasm (n = 1), pancreatic insulinoma (n = 1), pancreatic ductal adenocarcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). OTHERS (N = 4): Pancreatic cyst (n = 3) and annular pancreas (n = 1).

CONCLUSION: Paediatric pancreatic disease spans a wide spectrum of both benign and malignant disease and benefits from access to specialist medical, surgical, endoscopic, and interventional radiology expertise. Referrals for paediatric pancreatitis are increasing, but aetiology is different to that seen in adults.

LEVEL OF EVIDENCE: IV.

PMID:37957099 | DOI:10.1016/j.jpedsurg.2023.10.035

Secretory Conservation in Insulin Producing Cells: Is There a System-Level Law of Mass Action in Biology?

Fetched: November 14th, 2023, 5:02am GMT by None Firdos

ACS Omega. 2023 Sep 27;8(40):37573-37583. doi: 10.1021/acsomega.3c06058. eCollection 2023 Oct 10.

ABSTRACT

Altered secretion of insulin from pancreatic β-cells can manifest into disorders. For example, a lack of endogenously produced and/or secreted insulin results in Type 1 diabetes (and other associated subtypes). Pancreatic β-cells are the endocrine secretory cells that promote insulin secretion in response to glucose stimulation. Secretion in response to extracellular triggers is an interplay among various signaling pathways, transcription factors, and molecular mechanisms. The Mouse Insulinoma 6 (MIN6) cell line serves as a model system for gaining mechanistic insights into pancreatic β-cell functions. It is obvious that higher glucose consumption and increased insulin secretion are correlated. However, it has been reported that intracellular ATP levels remain ∼ constant beyond the extracellular glucose (EG) concentration of 10 mM. Therefore, any cause-effect relationship between glucose consumption (GC) and enhanced insulin secretion (eIS) remains unclear. We also found that total cellular protein, as well as total protein content in the culture "supernatant," remains constant regardless of varying EG concentrations. This indicated that eIS may be at the cost of (a) intracellular synthesis of other proteins and (b) secretion of other secretory proteins, or both (a) and (b), somehow coupled with GC by cells. To gain insights into the above, we carried out a transcriptome study of MIN6 cells exposed to hypoglycemic (HoG = 2.8 mM EG) and hyperglycemic (HyG = 25 mM EG) conditions. Expression of transcripts was analyzed in terms of Fragments Per Kilobase of transcript per Million mapped reads and Transcripts Per Million (FPKM and TPM) as well as values obtained by normalizing w.r.t. "∑(FPKM)" and "∑(TPM)." We report that HyG extracellular conditions lead to an ∼2-fold increase in insulin secretion compared to HoG measured by the enzyme-linked immunosorbent assay (ELISA) and transcripts of secreted proteins as well as their isoforms decreased in HyG conditions compared to HoG. Our results show for the first time that eIS in HyG conditions is at the cost of reduced transcription of other secreted proteins and is coupled with higher GC. The higher GC at increased extracellular glucose also indicates a yet undiscovered role of glucose molecules enhancing insulin secretion, since ATP levels resulting from glucose metabolism have been reported to be constant above an EG concentration of 10 mM. While extrapolation of our results to clinical implications is ambitious at best, this work reports novel cellular level aspects that seem relevant in some clinical observations pertaining to Type 1 diabetes. In addition, the conservatory nature of cellular secretions in insulin-secreting cells, discovered here, may be a general feature in cell biology.

PMID:37954232 | PMC:PMC10635588 | DOI:10.1021/acsomega.3c06058

Permalink for 'Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic β cells'

Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic β cells

Fetched: November 13th, 2023, 5:02am GMT by Achanta Rishisree

Biophys Chem. 2023 Oct 31;304:107130. doi: 10.1016/j.bpc.2023.107130. Online ahead of print.

ABSTRACT

Impeding or reducing human amylin aggregation and/or its toxicity can be key to preventing pancreatic islet amyloidosis and β-cell loss in patients with Type 2 Diabetes Mellitus (T2DM). Here, Punica granatum (pomegranate) peel, Sideritis raeseri (ironwort) and Aronia melanocarpa (chokeberry) leaf extracts, were tested for their novel anti-aggregative and antitoxic properties in human amylin (hIAPP) treated rat pancreatic insulinoma (INS) cells. The protein aggregation (Th-T) assay revealed an inhibitory trend of all three plant extracts against amylin aggregates. In agreement with this finding, pomegranate peel and ironwort extracts effectively prevented the transition of hIAPP from disordered, random coil structures into aggregation prone β-sheet enriched molecular assemblies, revealed by CD spectroscopy. Consistent with their anti-aggregative action, all three extracts prevented, to various degrees, reactive oxygen species (ROS) accumulation, mitochondrial stress, and, ultimately, apoptosis of INS cells. Collectively, the results from this study demonstrate effectiveness of natural products to halt hIAPP aggregation, redox stress, and toxicity, which could be exploited as novel therapeutics against amylin-derived islet amyloidosis and β-cell stress in T2DM.

PMID:37952497 | DOI:10.1016/j.bpc.2023.107130

Transformation of pancreatic nonfunctioning neuroendocrine tumor into metastatic insulinoma: A rare case report

Fetched: November 10th, 2023, 5:02am GMT by Venkata S Buddhavarapu

Clin Case Rep. 2023 Nov 6;11(11):e8152. doi: 10.1002/ccr3.8152. eCollection 2023 Nov.

ABSTRACT

Pancreatic neuroendocrine tumors can be classified as functional or nonfunctional based on hormone secretion. Management of each entity is different, with nonfunctional tumors being treated with traditional chemotherapy while functional tumors respond well to antihormonal therapy and immunologic agents. The conversion of one nonfunctional tumor into a functional tumor is an exceedingly rare event that complicates the overall management of these patients. In this report, we present the case of a 73-year-old woman who developed the conversion from a nonfunctional into a functional tumor and discuss the management options considered.

PMID:37942181 | PMC:PMC10627923 | DOI:10.1002/ccr3.8152

Dr. Allen Oldfather Whipple (1881-1963): Namesake of the pancreaticoduodenectomy

Fetched: November 10th, 2023, 5:02am GMT by Ashton D Hall

J Med Biogr. 2023 Nov 9:9677720231197430. doi: 10.1177/09677720231197430. Online ahead of print.

ABSTRACT

Allen O. Whipple was an American surgeon who popularized the pancreaticoduodenectomy (Whipple procedure) for periampullary cancer, which remains the gold standard for pancreatic tumor resections. Whipple was educated at Princeton University (B.S., 1904) and Columbia University College of Physicians and Surgeons (M.D., 1908). He swiftly ascended the academic ranks, culminating in his appointment as Professor of Surgery at Columbia and Director of Surgical Services at Presbyterian Hospital in 1921. Whipple published three criteria (Whipple's triad) for evaluating hyperinsulinism secondary to pancreatic insulinoma. He also revived interest in portocaval anastomosis to reduce portal hypertension, determining it to be a consequence of liver disease. During his 40-year career, Whipple introduced the concept of multidisciplinary teams and prospective data collection. He also shaped the structure of surgical training as President of the American Surgical Association and Chairman of the American Board of Surgery. Beyond the walls of the operating room, Whipple was a Renaissance Man whose childhood in Persia (Iran) engendered a lifelong interest in the region's art, culture, history, and medicine. Dr. Allen Oldfather Whipple is remembered as a pioneering physician and surgeon beloved by those who trained under him.

PMID:37941365 | DOI:10.1177/09677720231197430

Endoscopic ultrasound-guided ethanol ablation versus surgical resection of insulinomas

Fetched: November 7th, 2023, 5:02am GMT by Christian Jürgensen

Ultraschall Med. 2023 Nov 6. doi: 10.1055/a-2204-5814. Online ahead of print.

ABSTRACT

PURPOSE: Insulinoma is a rare tumor of the pancreas that can lead to hypoglycemia. To date, standard therapy is surgical resection. After first case report of successful endoscopic ultrasound-guided (EUS) ethanol injection 16 years ago, the need of establishing an alternative treatment method is unchanged facing the high morbidity rates of surgery and its inapplicability in some patients.

MATERIALS AND METHODS: Here, we provide retrospective data from 33 insulinoma patients that were treated at our center between 2010 and 2021. Of these, 9 patients were treated with EUS-guided ethanol injection and 24 underwent pancreatic surgery.

RESULTS: The ethanol group was older (ethanol: mean±SE 67.8±11.2 years vs. surgery: 52.3±15.7, p=0.014) with a higher Charlson Comorbidity Index (3.0 (1.0;4.0) vs. 1.0 (0.0;2.0), p=0.008). Lowest glucose values were similar between groups before (ethanol: 2.09±0.17 mmol/l vs. surgery: 1.81±0.08, p=0.158) and after (4.95±0.74 vs. 5.41±0.28, p=0.581) the respective treatments. Complications occurred more frequently in the surgery group (11 % vs. 54 %, p=0.026). One patient after prior partial pancreatectomy died postoperatively. Hospitalization time was significantly shorter in the ethanol group (4.78±0.78 days vs. 19.88±4.07, p<0.001).

CONCLUSION: EUS-guided ethanol injection can be similarly effective for the treatment of hyperinsulinemic hypoglycemia compared with pancreatic surgery but seems to be associated with less severe complications. This implies the need for prospective randomized trials in insulinoma patients with low risk for malignancy. Ziel: Insulinome sind seltene Tumore des Pankreas, die zu Hypoglykämien führen können. Die chirurgische Resektion ist aktuell Standardtherapie. Nach der ersten Fallbeschreibung einer erfolgreichen EUS-gesteuerten Alkoholinjektion vor 16 Jahren besteht unverändert der Bedarf einer Behandlungsalternative angesichts der hohe operativen Morbidität und der fehlenden Anwendbarkeit bei einigen Patienten. Material und Methode: Wir zeigen die retrospektiven Daten von 33 Insulinom-Patienten, die in unserem Zentrum zwischen 2010 und 2021 behandelt wurden. Von diesen wurden 9 Patienten durch EUS-geführte Alkohol-Injektion und 24 durch Pankreas-Chirurgie behandelt. Ergebnisse: Die Alkohol-Therapie-Gruppe war älter (Alkohol: median±SE 67.8±11.2 Jahre vs. Chirurgie: 52.3±15.7, p=0.014) mit einem höheren Charlson Comorbidity Index (3.0 (1.0;4.0) vs. 1.0 (0.0;2.0), p=0.008). Die niedrigsten Blutzucker waren in beiden Gruppen gleich vor (Alkohol: 2.09±0.17 mmol/l vs. Chirurgie: 1.81±0.08, p=0.158) und nach (4.95±0.74 vs. 5.41±0.28, p=0.581) den jeweiligen Behandlungen. Komplikationen traten häufiger in der Chirurgie-Gruppe auf (11 % vs. 54 %, p=0.026). Ein Patient starb nach partieller Pankreatektomie postoperativ. Die Krankenhausverweildauer war signifikant kürzer in der Alkohol-Gruppe (4.78±0.78 Tage vs. 19.88±4.07, p<0.001). Schlussfolgerungen: Die EUS-gesteuerte Alkoholinjektion kann gleich effektiv sein wie Chirurgie für die Behandlung der hyperinsulinämen Hypoglykämie, scheint aber mit weniger schweren Komplikationen assoziiert zu sein. Hieraus ergibt sich die Notwendigkeit für randomisierte Studien bei Insulinom-Patienten mit niedrigem Malignitäts-Risiko.

PMID:37931914 | DOI:10.1055/a-2204-5814

PP2Ac knockdown attenuates lipotoxicity‑induced pancreatic β‑cell dysfunction and apoptosis

Fetched: November 7th, 2023, 5:02am GMT by Zhengwei Zhang

Exp Ther Med. 2023 Oct 10;26(6):549. doi: 10.3892/etm.2023.12247. eCollection 2023 Dec.

ABSTRACT

Protein phosphatase 2A (PP2A) is one of the most common serine/threonine phosphatases in mammalian cells, and it primarily functions to regulate cell signaling, glycolipid metabolism and apoptosis. The catalytic subunit of PP2A (PP2Ac) plays an important role in the functions of the protein. However, there are few reports on the regulatory role of PP2Ac in pancreatic β-cells under lipotoxic conditions. In the present study, mouse insulinoma 6 (MIN6) pancreatic cells were transfected with short hairpin RNAs to generate PP2Ac knockdown cells and incubated with palmitate (PA) to establish a lipotoxicity model. Serine/threonine phosphatase assay system, Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay and western blotting were used to measure PP2A activity, cell viability, apoptosis, oxidative stress and insulin secretion in the cells. In addition, a mouse model of lipotoxicity was established with a high-fat diet (HFD) and the knockdown of PP2Ac using adeno-associated viruses to interfere with PP2Ac expression in the pancreatic tissues. The activity of PP2A in the mouse pancreatic tissue and the serum insulin level were measured. Furthermore, the proliferation of mouse pancreatic β-cells was assessed using pancreatic tissue immunofluorescence. PP2Ac knockdown inhibited lipotoxicity-induced PP2A hyperactivation, increased the resistance of pancreatic β-cells to lipotoxicity and attenuated PA-induced apoptosis in MIN6 cells. It also protected the endoplasmic reticulum and mitochondria, and ameliorated insulin secretion. The results of mRNA sequencing and western blotting analysis suggested that the protective effects of PP2Ac knockdown in MIN6 cells may be mediated via the MAPK pathway. Moreover, the results of the animal experiments suggested that specific knockdown of pancreatic PP2Ac effectively attenuated HFD-induced insulin resistance and reduced the compensatory proliferation of pancreatic β-cells in mice. In summary, the present study revealed the effects of interfering with PP2Ac gene expression on pancreatic β-cells in vivo and in vitro and the underlying mechanisms, which may provide insights for the treatment of type 2 diabetes mellitus in the clinic.

PMID:37928506 | PMC:PMC10623214 | DOI:10.3892/etm.2023.12247

Approach to the patient: Insulinoma

Fetched: November 6th, 2023, 5:02am GMT by Johannes Hofland

J Clin Endocrinol Metab. 2023 Oct 31:dgad641. doi: 10.1210/clinem/dgad641. Online ahead of print.

ABSTRACT

Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms (panNEN) with an estimated incidence of 1-4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with Whipple's triad: 1) symptoms, signs, or both consistent with hypoglycemia, 2) a low plasma glucose measured at the time of the symptoms and signs, and 3) relief of symptoms and signs when the glucose is raised to normal. Non-metastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive". The 5-years-survival of patients with an indolent insulinoma has been reported to be 94-100% and for patients with an aggressive insulinoma this amounts to 24-67%. Five-10% of insulinomas are associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by CT is followed by EUS or magnetic resonance imaging (MRI) for indolent, localized insulinomas. Glucagon-like peptide 1 receptor (GLP-1R) PET/CT or PET/MRI is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for the control of the hypoglycemias. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, Everolimus, Sunitinib and cytotoxic chemotherapy can be valuable options.

PMID:37925662 | DOI:10.1210/clinem/dgad641

Diagnostic work-up and surgical management of insulinoma: A retrospective analysis from a tertiary referral center

Fetched: November 3rd, 2023, 5:02am GMT by Valentina Andreasi

J Neuroendocrinol. 2023 Dec;35(12):e13353. doi: 10.1111/jne.13353. Epub 2023 Nov 2.

ABSTRACT

Insulinoma is a multifaceted disease that poses several challenges in terms of clinical presentation, diagnostic work-up, and surgical management. The aim of this study was to describe diagnostic work-up, surgical management, and postoperative outcomes of patients with insulinoma. All consecutive patients who underwent surgery for insulinoma at San Raffaele Hospital (Milan, Italy) between January 2008 and January 2022 were included. Overall, 98 patients were considered. The median delay between presenting symptoms and insulinoma diagnosis was 10 months (IQR, 4-21). Insulinoma diagnosis was made at our Institution in 45 patients, 20 of whom referred within 6 months from symptoms onset. In this subgroup, the median interval between symptoms presentation and insulinoma diagnosis was 4 months (IQR, 2-6), as compared to 14 months (IQR, 10-26) in patients (n = 25) who referred to our institution after 6 months from symptoms onset (p < .001). The insulinoma was localized preoperatively in all the cases. All patients underwent ≥1 high-quality imaging: computed tomography (CT: n = 87, sensitivity 84%), magnetic resonance imaging (MRI: n = 55, sensitivity 85%) and endoscopic ultrasound (EUS: n = 79, sensitivity 100%). MRI identified the tumor in eight patients with negative CT. EUS localized the insulinoma in three patients with negative CT and negative MRI. Parenchyma-sparing resections were performed in 41 patients. Contact with major vessels, lesion close to Wirsung duct and suspect of malignancy were the main reasons to perform a formal resection. An early referral to high-volume centers is important for reducing diagnostic delay in patients with insulinoma. The diagnostic work-up of insulinoma frequently requires several imaging modalities to be performed, with EUS being the most sensitive one. Parenchyma-sparing surgery for insulinoma should be performed whenever technically and oncologically feasible.

PMID:37915303 | DOI:10.1111/jne.13353

Recurrent Hypoglycemia Secondary to Insulinoma in an Adult With Beckwith-Wiedemann Syndrome

Fetched: November 2nd, 2023, 5:02am GMT by Tugce Akcan

JCEM Case Rep. 2023 Jun 28;1(3):luad062. doi: 10.1210/jcemcr/luad062. eCollection 2023 May.

ABSTRACT

Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder characterized by genetic and epigenetic changes on the chromosome 11p15.5 region, which includes genes that are important for fetal and postnatal growth. Children with BWS have a higher chance of having hypoglycemia, hyperinsulinemia, and malignancies early in life, although hypoglycemia caused by an insulinoma that develops later in life has not been reported. We describe the diagnosis of insulinoma in a 53-year-old man with BWS in this case report. This is the first case report of insulinoma in an adult with this syndrome.

PMID:37908580 | PMC:PMC10580426 | DOI:10.1210/jcemcr/luad062

Insulinoma Presenting With Postprandial Hypoglycemia in a Pregnant Woman With MEN-1

Fetched: November 2nd, 2023, 5:02am GMT by Anna J Wood

JCEM Case Rep. 2022 Nov 30;1(1):luac015. doi: 10.1210/jcemcr/luac015. eCollection 2023 Jan.

ABSTRACT

Insulinomas are rare insulin-secreting tumors of pancreatic origin that cause hypoglycemia and can be associated with multiple endocrine neoplasia type 1 (MEN1). While rare, they are the most common cause of hypoglycemia related to endogenous hyperinsulinism. A 28-year-old woman with known MEN1 presented with postprandial hypoglycemia in the second trimester of pregnancy. Prior to her presentation she was known to have several pancreatic neuroendocrine tumors that had been stable on serial imaging, but no history of hypoglycemia. She was managed with dietary intervention during pregnancy and gave birth to a healthy baby at 37 weeks' gestation. After pregnancy, hypoglycemia initially resolved, but then recurred at 8 months post partum. Magnetic resonance imaging showed several pancreatic neoplasms with the largest lesion measuring 29 mm in the pancreatic tail, unchanged from previous imaging. After localization with a selective arterial calcium stimulation test, the patient underwent successful distal pancreatectomy with resolution of symptoms. This case is unusual in that her initial presentation was during pregnancy, she had predominantly postprandial rather than fasting hypoglycemia, and her symptoms remitted for several months after delivery. Key learning points are to have a low index of suspicion for an insulinoma when there is a history of MEN1 and the need for a pragmatic approach to diagnosis and treatment during pregnancy.

PMID:37908256 | PMC:PMC10578399 | DOI:10.1210/jcemcr/luac015

Synchronous Insulinoma and Glucagonoma: A Review of the Literature

Fetched: November 1st, 2023, 5:01am GMT by Christos Damaskos

In Vivo. 2023 Nov-Dec;37(6):2402-2408. doi: 10.21873/invivo.13345.

ABSTRACT

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas.

MATERIALS AND METHODS: A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study.

RESULTS: A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021.

CONCLUSION: Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.

PMID:37905620 | PMC:PMC10621456 | DOI:10.21873/invivo.13345

Clinicopathological Features of Insulinoma: A Single Tertiary Center Experience

Fetched: October 31st, 2023, 5:02am GMT by Mehmet Sözen

Indian J Surg Oncol. 2023 Sep;14(3):564-570. doi: 10.1007/s13193-023-01774-0. Epub 2023 May 23.

ABSTRACT

Insulinoma is a rare pancreatic neuroendocrine tumor with an incidence of 1-4 cases per million. Here we present our 10 years of experience in 13 cases of insulinoma. We retrospectively reviewed all insulinoma patients diagnosed and treated between 2012 and 2022. Clinical and pathological features, diagnostic methods, and follow-up results of insulinoma patients were discussed. A total of 13 patients were included in this study (7 men, and 6 women). The mean age at the time of diagnosis was 58 (36.5-70.5) years. There is only one patient diagnosed with MEN-1 syndrome. The mean time from the onset of symptoms to the diagnosis was 15 (7-27.5) months. In the prolonged fasting test, symptomatic hypoglycemia occurred in all patients within 48 h. The median size of lesions was 15 (12-24) mm, and 46.2% of these lesions were isolated in the pancreatic tail. Ga-68 DOTATATE PET/CT detected lesions with 100% accuracy. Three patients met the criteria for malignant insulinoma. Octreotide LAR was given to 1 patient with metastatic disease and 1 patient who did not accept surgery. The metastatic patient received 8 cycles of Lu treatment and died after 51 months of follow-up. The diagnosis of insulinoma can be challenging. The 48-h fasting test period provided sufficient information for the diagnosis of insulinoma. Ga-68 DOTATATE PET/CT may be an alternative in cases where cross-sectional imaging cannot localize the pancreatic lesion.

PMID:37900637 | PMC:PMC10611634 | DOI:10.1007/s13193-023-01774-0

Clinical Case Report of Non-Diabetic Hypoglycemia Due to a Combination of Germline Mutations in the MEN1 and ABCC8 Genes

Fetched: October 29th, 2023, 5:02am GMT by Marina Yukina

Genes (Basel). 2023 Oct 17;14(10):1952. doi: 10.3390/genes14101952.

ABSTRACT

INTRODUCTION: Non-diabetic hypoglycemia (NDH) is a collective term including the multiple causes of hypoglycemic syndrome not due to diabetes mellitus. NDH may result from insulinoma, IGF-2-omas, hypocorticism, Hirata's disease, genital disorders of glucose metabolism, etc. One of the most common causes of NDH faced by an endocrinologist is insulinoma, which in turn can be part of the hereditary syndrome of multiple endocrine neoplasia type 1 (MEN1). Congenital disorders of glucose metabolism in adult patients, on the contrary, are diagnosed extremely rarely, since they usually manifest in childhood. This article presents a unique clinical case of a patient with NDH and genetically verified MEN1 in combination with congenital hyperinsulinism due to an ABCC8 gene mutation.

CASE REPORT: A 43-year-old patient with hypoglycemic symptoms from childhood is presented, in whom multiple pancreatic tumors and fluctuations in glycemia from 38.7 mg/dL to 329.7 mg/dL (2.15 to 18.3 mmol/L) were detected in adulthood, but a mild course of hypoglycemic syndrome was noted. Numerous examinations that were performed to establish an accurate diagnosis are described, signs that served as a reason for expanding the complex of studies are indicated, possible pathogenetic mechanisms of the mild course of hypoglycemic syndrome and hyperglycemic conditions are discussed.

CONCLUSION: This case report is original and highlights that we must always remain intolerant of the inexplicable. Conducting an extended gene study can help perform a correct diagnosis in complex cases.

PMID:37895301 | PMC:PMC10606354 | DOI:10.3390/genes14101952

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs

Fetched: October 29th, 2023, 5:02am GMT by Atsushi Yamashita

Int J Mol Sci. 2023 Oct 23;24(20):15466. doi: 10.3390/ijms242015466.

ABSTRACT

Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.

PMID:37895146 | PMC:PMC10607179 | DOI:10.3390/ijms242015466

Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas

Fetched: October 29th, 2023, 5:02am GMT by Tiina Vesterinen

Int J Mol Sci. 2023 Oct 13;24(20):15164. doi: 10.3390/ijms242015164.

ABSTRACT

Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1-5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients.

PMID:37894845 | PMC:PMC10606800 | DOI:10.3390/ijms242015164

Permalink for 'Pancreatic Neuroendocrine Tumors in MEN1 Patients: Difference in Post-Operative Complications and Tumor Progression between Major and Minimal Pancreatic Surgeries'

Pancreatic Neuroendocrine Tumors in MEN1 Patients: Difference in Post-Operative Complications and Tumor Progression between Major and Minimal Pancreatic Surgeries

Fetched: October 29th, 2023, 5:02am GMT by Francesco Tonelli

Cancers (Basel). 2023 Oct 10;15(20):4919. doi: 10.3390/cancers15204919.

ABSTRACT

Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but the real immediate and long-term therapeutic benefit of a partial extensive pancreatic resection remains controversial. We analyzed, in 43 PNEN MEN1 patients who underwent 19 pancreaticoduodenectomies (PD), 19 distal pancreatectomies (DP), and 5 minimal pancreatectomies, the prevalence of surgery-derived early complications and post-operative pancreatic sequelae, and the PNEN relapse-free survival time after surgery, comparing major (PD+DP) and minimal pancreatic surgeries. No post-operative mortality was observed. Metastatic cancers were found in 12 cases, prevalently from duodenal gastrinoma. Long-term cure of endocrine syndromes, by the 38 major pancreatic resections, was obtained in 78.9% of gastrinomas and 92.9% of insulinomas. In only one patient, hepatic metastases, due to gastrinoma, progressed to death. Out of the 38 major surgeries, only one patient was reoperated for the growth of a new PNEN in the remnant pancreas. No functioning PNEN persistence was reported in the five minimal pancreatic surgeries, PNEN relapse occurred in 60% of patients, and 40% of cases needed further pancreatic resection for tumor recurrence. No significant difference in PNEN relapse-free survival time after surgery was found between major and minimal pancreatic surgeries.

PMID:37894286 | PMC:PMC10605506 | DOI:10.3390/cancers15204919

$Permalink for 'More on Anti-Insulin Receptor Antibody in Malignant Insulinoma and Refractory Hypoglycemia. Reply'$

More on Anti-Insulin Receptor Antibody in Malignant Insulinoma and Refractory Hypoglycemia. Reply

Fetched: October 28th, 2023, 5:02am GMT by Soravis Osataphan

N Engl J Med. 2023 Oct 26;389(17):1635. doi: 10.1056/NEJMc2311041.

NO ABSTRACT

PMID:37888936 | DOI:10.1056/NEJMc2311041

$Permalink for 'More on Anti-Insulin Receptor Antibody in Malignant Insulinoma and Refractory Hypoglycemia'$

More on Anti-Insulin Receptor Antibody in Malignant Insulinoma and Refractory Hypoglycemia

Fetched: October 28th, 2023, 5:02am GMT by Louis Schubert

N Engl J Med. 2023 Oct 26;389(17):1634-1635. doi: 10.1056/NEJMc2311041.

NO ABSTRACT

PMID:37888935 | DOI:10.1056/NEJMc2311041

Homeostasis Model Assessment of β-Cell Function for Diagnosis of Insulinoma

Fetched: October 28th, 2023, 5:02am GMT by Kálmán Bódis

J Clin Endocrinol Metab. 2023 Oct 27:dgad618. doi: 10.1210/clinem/dgad618. Online ahead of print.

ABSTRACT

CONTEXT: Diagnosis of insulinoma is based on different criteria from the 72-hour fasting test according to current guidelines (Endocrine Society [ES], European [ENETS], and North American [NANETS] Neuroendocrine Tumor Societies), including assessment of β-cell function by glucagon stimulation test.

OBJECTIVE: This study tested whether the homeostasis model assessment of insulin secretion, including assessment of β-cell function, (HOMA-B) at the end of the fasting test provides comparable efficacy for insulinoma diagnosis.

METHODS: In 104 patients with suspected insulinoma, 72-hour fasting tests were performed with frequent assessment of glucose, insulin, and C-peptide in venous blood. HOMA-B values using insulin and C-peptide were calculated at the end of the fasting test, as defined by the lowest glucose concentration from each participant.

RESULTS: HOMA-B was more than 6.5-fold higher in patients with (n = 23) than in those without (n = 81) insulinoma (insulin and C-peptide; both P < .001). HOMA-B (cutoff using insulin >253 a.u. and C-peptide >270 a.u.) had a sensitivity of 0.96, 0.78 to 1.00, and a specificity of 0.96 or greater (≥0.89-0.99) for insulinoma diagnosis. ES and ENETS/NANETS criteria reached a diagnostic sensitivity of less than or equal to 0.96 (≤0.78-1.00) and ≤0.83 (≤0.61-0.95) as well as specificity of ≤0.85 (≤0.76-0.92) and less than or equal to 1.00 (≤0.96-1.00) for insulin, and C-peptide, respectively. Using insulin for HOMA-B, sensitivity tended to be higher compared to ENETS/NANETS criteria (P = .063) and specificity was higher compared to ES criteria using insulin and C-peptide (both P < .005).

CONCLUSION: HOMA-B, as calculated at the end of the fasting test employing defined cutoffs for insulin and C-peptide, provides excellent diagnostic efficacy, suggesting that it might represent an alternative and precise tool to diagnose insulinoma.

PMID:37888878 | DOI:10.1210/clinem/dgad618

Production and antigenicity analysis of a recombinant insulinoma associated protein-2 in HEK293 cells

Fetched: October 26th, 2023, 5:02am GMT by Jingwen Qian

Sheng Wu Gong Cheng Xue Bao. 2023 Oct 25;39(10):4246-4257. doi: 10.13345/j.cjb.230087.

ABSTRACT

Insulinoma-associated protein-2 (IA-2) is a transmembrane glycoprotein belonging to the tyrosine phosphatase-like protein family as well as an important autoantigen in the diagnosis of type 1 diabetes. IA-2 products have been marketed in Europe and the United States. At present, commercially available IA-2 antigens are either the recombinant IA-2ic domain or the IA-2 naturally extracted from bovine islets. However, the recombinant IA-2 antigen displays weak positive in clinic practice, which often results in occasional detection failures, thus cannot completely replace the naturally extracted IA-2 antigen. In this study, an HEK293 expression system was used to explore the production of recombinant IA-2. An IA-2 transmembrane fragment (IA-2 TMF) located at amino acid position 449-979, also known as the natural membrane protein form of IA-2, was produced in HEK293 through transfection, and both the expression conditions and dissolution conditions of the membrane protein were also optimized. The purified membrane protein yield was 0.78 mg/L cell culture. Subsequently, the antigen activity of IA-2 TMF was compared with RSR rhIA-2 through enzyme linked immunosorbent assay. The serum of 77 type 1 diabetes patients and 32 healthy volunteers were detected. Receiver operating characteristic curve (ROC) curve was used to characterize the sensitivity and specificity of the test results. The results showed that the sensitivity of IA-2 TMF was 71.4% (55/77), while the sensitivity of RSR rhIA-2 was 63.6% (49/77), and the specificity of both antigens were all 100%. There was no significant difference in specificity between the two antigens, but the sensitivity of IA-2 TMF was appreciably better than that of the imported gold standard RSR rhIA-2 antigen. In conclusion, the recombinant IA-2 TMF produced in HEK293 cells can be used as a raw material to develop in vitro diagnostic reagents for type 1 diabetes.

PMID:37877403 | DOI:10.13345/j.cjb.230087

Using a modular massively parallel reporter assay to discover context-specific regulatory grammars in type 2 diabetes

Fetched: October 25th, 2023, 5:02am GMT by Adelaide Tovar

bioRxiv. 2023 Oct 10:2023.10.08.561391. doi: 10.1101/2023.10.08.561391. Preprint.

ABSTRACT

Recent genome-wide association studies have established that most complex disease-associated loci are found in noncoding regions where defining their function is nontrivial. In this study, we leverage a modular massively parallel reporter assay (MPRA) to uncover sequence features linked to context-specific regulatory activity. We screened enhancer activity across a panel of 198-bp fragments spanning over 10k type 2 diabetes- and metabolic trait-associated variants in the 832/13 rat insulinoma cell line, a relevant model of pancreatic beta cells. We explored these fragments' context sensitivity by comparing their activities when placed up-or downstream of a reporter gene, and in combination with either a synthetic housekeeping promoter (SCP1) or a more biologically relevant promoter corresponding to the human insulin gene ( INS ). We identified clear effects of MPRA construct design on measured fragment enhancer activity. Specifically, a subset of fragments (n = 702/11,656) displayed positional bias, evenly distributed across up- and downstream preference. A separate set of fragments exhibited promoter bias (n = 698/11,656), mostly towards the cell-specific INS promoter (73.4%). To identify sequence features associated with promoter preference, we used Lasso regression with 562 genomic annotations and discovered that fragments with INS promoter-biased activity are enriched for HNF1 motifs. HNF1 family transcription factors are key regulators of glucose metabolism disrupted in maturity onset diabetes of the young (MODY), suggesting genetic convergence between rare coding variants that cause MODY and common T2D-associated regulatory variants. We designed a follow-up MPRA containing HNF1 motif-enriched fragments and observed several instances where deletion or mutation of HNF1 motifs disrupted the INS promoter-biased enhancer activity, specifically in the beta cell model but not in a skeletal muscle cell line, another diabetes-relevant cell type. Together, our study suggests that cell-specific regulatory activity is partially influenced by enhancer-promoter compatibility and indicates that careful attention should be paid when designing MPRA libraries to capture context-specific regulatory processes at disease-associated genetic signals.

PMID:37873175 | PMC:PMC10592691 | DOI:10.1101/2023.10.08.561391

Long-term clinical and radiological outcomes of endoscopic ultrasound-guided radiofrequency ablation of benign insulinomas

Fetched: October 22nd, 2023, 5:02am GMT by Zoé Debraine

Clin Endocrinol (Oxf). 2023 Oct 20. doi: 10.1111/cen.14981. Online ahead of print.

ABSTRACT

OBJECTIVE: In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative nonsurgical treatment for pancreatic neuroendocrine tumours. The aim of our study was to assess the long-term follow-up of patients treated with EUS-RFA for a sporadic insulinoma in our centre in terms of efficacy, safety and risk of recurrence.

DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed the data of 11 patients with an insulinoma treated by EUS-RFA in our tertiary centre between June 2018 and April 2022. Clinical and biological, as well as imaging, follow-up was planned at 3, 6, 12 months and then annually.

RESULTS: In our series, there were nine women and two men with a median age of 65 years. All tumours were sporadic, with a mean size of 11 mm. The procedure allowed an immediate and complete symptomatic and biological remission in all patients without notable complications. Complete radiological resolution of the tumour after ablation was observed in seven patients, and persistence of an asymptomatic tumour residue was observed in four patients. During the mean follow-up period of 26 months, two patients presented a significant but asymptomatic increase of the tumour residue; a second EUS-RFA session was performed in one patient and the other patient is being closely monitored.

CONCLUSIONS: EUS-RFA treatment of benign insulinomas provides a long-term complete clinical resolution of hypoglycaemia. A long-term follow-up is essential if residual tumour persists after initial EUS-RFA treatment.

PMID:37859570 | DOI:10.1111/cen.14981

Metabolomic identification of biochemical changes induced by fluoxetine in an insulinoma cell line (MIN6)

Fetched: October 17th, 2023, 5:02am GMT by Surachai Ngamratanapaiboon

Res Pharm Sci. 2023 Aug 20;18(5):517-527. doi: 10.4103/1735-5362.383707. eCollection 2023 Sep-Oct.

ABSTRACT

BACKGROUND AND PURPOSE: The use of fluoxetine raises the risk of pancreatic beta-cell dysfunction. However, the specific mechanism behind its mechanism of action in beta cells is unknown. This study investigated the cellular response of MIN6 cells to fluoxetine using untargeted cell-based metabolomics.

EXPERIMENTAL APPROACH: Metabolic profiling of MIN6 cells was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses.

FINDINGS/RESULTS: Sixty-six metabolites that had been differentially expressed between the control and fluoxetine-treated groups demonstrated that the citric acid cycle is mainly perturbed by fluoxetine treatment.

CONCLUSION AND IMPLICATIONS: The current study provides insights into the molecular mechanisms of fluoxetine effects in MIN6 cells.

PMID:37842516 | PMC:PMC10568956 | DOI:10.4103/1735-5362.383707

Permalink for 'A Case of Insulinoma with Hyperprocalcitoninemia and Hypercalcitoninemia Showing Coexpression of Insulin and Calcitonin in Its Tumor Cells'

A Case of Insulinoma with Hyperprocalcitoninemia and Hypercalcitoninemia Showing Coexpression of Insulin and Calcitonin in Its Tumor Cells

Fetched: October 16th, 2023, 5:02am GMT by Tomoko Kaketaka

Intern Med. 2023 Oct 13. doi: 10.2169/internalmedicine.1565-23. Online ahead of print.

ABSTRACT

Neuroendocrine neoplasms can produce multiple hormones that are released into the bloodstream, causing symptoms that vary depending on the type and quantity of hormones involved. We herein report a 63-year-old asymptomatic patient with pancreatic insulinoma who showed marked elevations in circulating calcitonin and procalcitonin levels that returned to normal following surgery. Immunohistochemical analyses confirmed the co-staining of calcitonin and insulin immunoreactivity in the tumor cells, suggesting a calcitonin-producing insulinoma. This insulinoma released calcitonin and a considerable amount of its precursor peptide, procalcitonin, resulting in both hyperprocalcitoninemia and hypercalcitoninemia.

PMID:37839887 | DOI:10.2169/internalmedicine.1565-23

Ethanol Ablation for Benign Insulinoma: Intraoperative and Endoscopic Approaches

Fetched: October 16th, 2023, 5:02am GMT by Alaa Sada

J Surg Res. 2024 Jan;293:663-669. doi: 10.1016/j.jss.2023.08.018. Epub 2023 Oct 13.

ABSTRACT

INTRODUCTION: Ethanol ablation can be utilized to manage insulinoma. We aimed to analyze our outcomes of endoscopic ultrasound (EUS) and intraoperative ultrasound (IOUS) guided Ethanol ablation of insulinoma.

METHODS: A single institution retrospective review of adults undergoing Ethanol ablation of benign pancreatic insulinoma (2007-2022) was performed. Outcomes were categorized as resolution of hypoglycemia, improvement, or no change at last follow-up.

RESULTS: A total of 16 patients underwent Ethanol ablation of benign insulinoma (N = 8 EUS, N = 8 IOUS): median age was 68 y, 8 (50%) were females, and 2 (12.5%) were associated with multiple endocrine neoplasia type-1. Median insulinoma size was 12 (range 7, 25) mm. Ethanol ablation was preferred over resection to avoid pancreaticoduodenectomy when it was not possible to enucleate the tumor in 10 (62.5%) patients while the rest underwent ablation due to being poor surgical candidates or because of a history of previous pancreatic resection. The median follow-up (interquartile range) was 43 (19.5, 81.5) mo. Resolution of hypoglycemia occurred in 11 patients (5 EUS, 6 IOUS), while the rest (3 EUS, 2 IOUS) experienced improvement in the severity and frequency of hypoglycemia. A single patient underwent resection following a previous ablation for symptomatic hypoglycemia 5 y after EUS guided ablation.

CONCLUSIONS: Ethanol ablation provides an alternative therapeutic option for patients with insulinoma. Both EUS and IOUS guided approaches are associated with a favorable resolution rate although EUS guided ablation may require multiple procedures to optimize outcomes.

PMID:37839097 | DOI:10.1016/j.jss.2023.08.018

Recurrence of solitary fibrous tumor of the pleura with hypoglycemia (Doege-Potter Syndrome): a case report description

Fetched: October 13th, 2023, 5:02am GMT by Chuxu Wang

Front Oncol. 2023 Sep 26;13:1245289. doi: 10.3389/fonc.2023.1245289. eCollection 2023.

ABSTRACT

Hypoglycemia has multiple causes, but the most common is a complication of insulin treatment. In addition to insulin therapy, tumors such as insulinomas of pancreatic origin and extrapancreatic tumors causing paraneoplastic syndromes should also be considered. Solitary fibrous tumors of the pleura (SFTP) is rare tumor, which when associated with hypoglycemia causes Doege-Potter syndrome. This article reports a case of a 69-year-old man with Doege-Potter syndrome and underwent the first surgical resection for SFTP. However, the tumor recurred 9 years later with hypoglycemic symptoms and implant metastasis. This recurrent tumor originated from the visceral pleura, was more aggressive and invaded the diaphragm and parietal pleura. After the second surgical removal of the tumor, the hypoglycemic symptoms disappeared.

PMID:37823058 | PMC:PMC10562620 | DOI:10.3389/fonc.2023.1245289

Alterations in intra- and inter-network connectivity associated with cognition impairment in insulinoma patients

Fetched: October 12th, 2023, 5:02am GMT by Hui Nong

Front Endocrinol (Lausanne). 2023 Sep 25;14:1234921. doi: 10.3389/fendo.2023.1234921. eCollection 2023.

ABSTRACT

OBJECTIVE: Cognitive dysfunction is common in insulinoma patients, but the underlying neural mechanisms are less well understood. This study aimed to explore the alterations of intra- and inter-network connectivity patterns associated with patients with insulinoma.

METHODS: Resting-state fMRI were acquired from 13 insulinoma patients and 13 matched healthy controls (HCs). Group Independent component analysis (ICA) was employed to capture the resting-state networks (RSNs), then the intra- and inter-network connectivity patterns, were calculated and compared. Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function. The relationship between connectivity patterns and MoCA scores was also examined.

RESULTS: Insulinoma patients performed significantly worse on MoCA compared to HCs. The intra-network connectivity analysis revealed that patients with insulinoma showed decreased connectivity in the left medial superior frontal gyrus within anterior default mode network (aDMN), and decreased connectivity in right lingual gyrus within the visual network (VN). The intra-network connectivity analysis showed that patients with insulinoma had an increased connectivity between the inferior-posterior default mode network (ipDMN) and right frontoparietal network (rFPN) and decreased connectivity between the ipDMN and auditory network (AUN). There was a significant negative correlation between the ipDMN-rFPN connectivity and MoCA score.

CONCLUSION: This study demonstrated significant abnormalities in the intra- and inter-network connectivity in patients with insulinoma, which may represent the neural mechanisms underlying the cognitive impairment in insulinoma patients.

PMID:37818091 | PMC:PMC10561291 | DOI:10.3389/fendo.2023.1234921

Permalink for 'Astragalus polysaccharide restores insulin secretion impaired by lipopolysaccharides through the protein kinase B /mammalian target of rapamycin/glucose transporter 2 pathway'

Astragalus polysaccharide restores insulin secretion impaired by lipopolysaccharides through the protein kinase B /mammalian target of rapamycin/glucose transporter 2 pathway

Fetched: October 11th, 2023, 5:03am GMT by Xiaodan Ren

BMC Complement Med Ther. 2023 Oct 10;23(1):358. doi: 10.1186/s12906-023-04188-1.

ABSTRACT

BACKGROUND: Lipopolysaccharide (LPS)-induced dysfunction of pancreatic β-cells leads to impaired insulin (INS) secretion. Astragalus polysaccharide (APS) is a bioactive heteropolysaccharide extracted from Astragalus membranaceus and is a popular Chinese herbal medicine. This study aimed to elucidate the mechanisms by which APS affects INS secretion from β-cells under LPS stress.

METHODS: Rat insulinoma (INS-1) cells were treated with LPS at a low, medium, or high concentration of APS. Glucose-stimulated insulin secretion (GSIS) was evaluated using an enzyme-linked immunosorbent assay (ELISA). Transcriptome sequencing was used to assess genome-wide gene expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the signaling pathways affected by APS. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to evaluate the gene expression of glucose transporter 2 (GLUT2), glucokinase (GCK), pancreatic duodenal homeobox-1 (PDX-1), and INS. Western blot analysis was used to detect the protein expression of phosphorylated protein kinase B (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), total mTOR (t-mTOR), and GLUT2.

RESULTS: LPS decreased GLUT2, GCK, PDX-1, and INS expression and reduced GSIS. These LPS-induced decreases in gene expression and GSIS were restored by APS treatment. In addition, transcriptome sequencing in combination with KEGG enrichment analysis revealed changes in the INS signaling pathway following APS treatment. LPS decreased p-Akt and p-mTOR expression, which was restored by APS treatment. The restorative effects of APS on GSIS as well as on the expression of GLUT2, GCK, PDX-1, and INS were abolished by treatment with the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin (RPM).

CONCLUSIONS: APS restored GSIS in LPS-stimulated pancreatic β-cells by activating the Akt/mTOR/GLUT2 signaling pathway.

PMID:37817130 | PMC:PMC10563267 | DOI:10.1186/s12906-023-04188-1

Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion

Fetched: October 10th, 2023, 5:03am GMT by Abigael Cheruiyot

bioRxiv. 2023 Sep 29:2023.09.29.560203. doi: 10.1101/2023.09.29.560203. Preprint.

ABSTRACT

Pancreatic β-cells are specialized for coupling glucose metabolism to insulin peptide production and secretion. Acute glucose exposure robustly and coordinately increases translation of proinsulin and proteins required for secretion of mature insulin peptide. By contrast, chronically elevated glucose levels that occur during diabetes impair β-cell insulin secretion and have been shown experimentally to suppress insulin translation. Whether translation of other genes critical for insulin secretion are similarly downregulated by chronic high glucose is unknown. Here, we used high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells to elucidate the genome-wide impact of sustained high glucose on β-cell mRNA translation. Prior to induction of ER stress or suppression of global translation, sustained high glucose suppressed glucose-stimulated insulin secretion and downregulated translation of not only insulin, but also of mRNAs related to insulin secretory granule formation, exocytosis, and metabolism-coupled insulin secretion. Translation of these mRNAs was also downregulated in primary rat and human islets following ex-vivo incubation with sustained high glucose and in an in vivo model of chronic mild hyperglycemia. Furthermore, translational downregulation decreased cellular abundance of these proteins. Our findings uncover a translational regulatory circuit during β-cell glucose toxicity that impairs expression of proteins with critical roles in β-cell function.

PMID:37808767 | PMC:PMC10557781 | DOI:10.1101/2023.09.29.560203

Exploring dual effects of dinutuximab beta on cell death and proliferation of insulinoma

Fetched: October 7th, 2023, 5:02am GMT by Ayse Karatug Kacar

Chem Biol Drug Des. 2023 Oct 6:e14368. doi: 10.1111/cbdd.14368. Online ahead of print.

ABSTRACT

Insulinoma INS-1 cells are pancreatic beta cell tumors. Dinutuximab beta (DB) is a monoclonal antibody used in the treatment of neuroblastoma. The aim of this study is to investigate the effects of DB on pancreatic beta cell tumors at the molecular level. DB (Qarziba®) was available from EUSA Pharma. Streptozotocin (STZ) was used induce to cell cytotoxicity. DB was applied to the cells before or after the STZ application. KCND3, KCNN4, KCNK1, and PTHrP gene expression levels were analyzed by q-RT-PCR, and protein levels were analyzed by Western blotting. Analysis of glucose-stimulated insulin secretion was performed. Ca⁺² and CA19-9 levels were determined by the ELISA kit. PERK, CHOP, HSP90, p-c-Jun, p-Atf2, and p-Elk1 protein levels were analyzed by simple WES. Decreased KCND3, KCNK1, and PTHrP protein levels and increased KCND3, KCNN4, KCNK1, and PTHrP gene expression levels were observed with DB applied after STZ application. Cell dysfunction was detected with DB applied before and after STZ application. Ca19-9 and Ca⁺² levels were increased with DB applied after STZ application. PERK, CHOP, and p-Elk1 levels decreased, while HSP90 levels increased with DB applied after STZ application. CHOP, p-Akt-2, and p-c-Jun levels increased in the DB group. As a result, INS-1 cells go to cell death via the ERK signaling pathway without ER stress and release insulin with the decrease of K+ channels and an increase in Ca⁺² levels with DB applied after STZ application. Moreover, the cells proliferate via JNK signaling with DB application. DB holds promise for the treatment of insulinoma. The study should be supported by in vivo studies.

PMID:37802653 | DOI:10.1111/cbdd.14368

Recurrent Non-islet Cell Tumor Hypoglycemia Secondary to Hepatocellular Carcinoma: Case Report and Literature Review

Fetched: October 7th, 2023, 5:02am GMT by Dan He

Z Gastroenterol. 2023 Oct 5. doi: 10.1055/a-2170-1691. Online ahead of print.

ABSTRACT

RATIONALE: Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome caused by tumors other than insulinoma that is primarily due to excessive production of insulin-like growth factor-II (IGF-II). The prevalence of NICTH is likely underestimated because of a lack of clinical recognition.

PATIENT CONCERNS: A 41-year-old male with massive malignant liver tumors presented with recurrent severe hypoglycemia, weight loss, and liver cirrhosis.

DIAGNOSIS: NICTH related to IGF-II produced by hepatocellular carcinoma was diagnosed based on clinical symptoms, biochemical tests, and elevated IGF-II/IGF-I ratio.

INTERVENTION: Initial treatment with intravenous glucose and parenteral nutrition showed limited efficacy. Glucocorticoids and recombinant human growth hormone led to progressive improvement in blood glucose levels.

OUTCOME: Due to extensive tumor burden and liver failure, surgical resection was not feasible, and the patient ultimately succumbed to refractory hypoglycemia and passed away in two weeks.

LESSONS: Early recognition and diagnosis of NICTH are crucial in patients with recurrent hypoglycemia and large tumors. Surgical resection is the preferred treatment option, but supportive care and pharmacological interventions, such as glucocorticoids and growth hormone, can help manage refractory hypoglycemia. Further research is needed to explore novel treatment options, including anti-IGF-I and -IGF-II neutralizing antibodies.

PMID:37798922 | DOI:10.1055/a-2170-1691

Permalink for 'The therapeutic effects of exosomes the first time isolated from pancreatic islet-derived progenitor cells in the treatment of pancreatic cancer'

The therapeutic effects of exosomes the first time isolated from pancreatic islet-derived progenitor cells in the treatment of pancreatic cancer

Fetched: October 6th, 2023, 5:02am GMT by Imren Hasoglu

Protoplasma. 2023 Oct 6. doi: 10.1007/s00709-023-01896-w. Online ahead of print.

ABSTRACT

Insulinoma is an excessive insulin-released beta cell tumor. Pancreas cancer is one of the deadliest malignant neoplasms. Exosomes are secreted cell membrane vesicles containing a large number of proteins, lipids, and nucleic acids. The aim of this study is to investigate the effects of exosomes on two cell lines of benign and malignant character. For the first time, exosomes were isolated from pancreatic island-derived progenitor cells (PID-PCs) and applied to INS-1 and MiaPaCa-2 cells. In addition, exosomes isolated from PID-PC, MiaPaca-2, and INS-1 cells were characterized in order to compare their sizes with other previously isolated exosomes. Alix, TSG101, CD9, and CD81 were analyzed. The size and concentration of exosomes and the cell viability were detected. The cells were marked with HSP90, HSF-1, Kaspaz-8, Active-Kaspaz-3, Beclin, and p-Bcl-2. The cell cytotoxicity and insulin levels kit were measured. Alix in all exosomes, and PID-PC, MiaPaca-2 cell lysates; TSG101 in PID-PC and MiaPaca-2 cell lysates; CD9 in INS-1 exosomes were detected. The dimensions of isolated exosomes were 103.6 ± 28.6 nm, 100.7 ± 10 nm, and 147.2 ± 12.3 nm for PID-PCs, MiaPaca-2, and INS-1 cells. The cell viability decreased and HSP90 increased in the MiaPaca-2 cells. The HSF-1 was higher in the control MiaPaca-2 cell compared to the control INS-1 cell, and the exosome-treated MiaPaca-2 cell compared to the exosome-treated INS-1 cell. Beclin and p-Bcl-2 were decreased in the exosome-treated MiaPaca-2 cells. The insulin level in the cell lysates increased compared to cell secretion in INS-1 cells. In conclusion, exosomes isolated from the PID-PC caused cell death in the MiaPaca-2 cells in a time- and dose-dependent manner. The IC50 value determined for MiaPaca-2 cells has no effect on cell viability in INS-1 cells, which best mimics pancreatic beta cells and can be used instead of healthy pancreatic beta cells. Isolated exosomes can kill cancer cells without damaging healthy cells.

PMID:37798610 | DOI:10.1007/s00709-023-01896-w

Theranostic in GLP-1R molecular imaging: challenges and emerging opportunities

Fetched: October 3rd, 2023, 5:02am GMT by Yang Xie

Front Mol Biosci. 2023 Sep 15;10:1210347. doi: 10.3389/fmolb.2023.1210347. eCollection 2023.

ABSTRACT

Theranostic in nuclear medicine combines diagnostic imaging and internal irradiation therapy using different therapeutic nuclear probes for visual diagnosis and precise treatment. GLP-1R is a popular receptor target in endocrine diseases, non-alcoholic steatohepatitis, tumors, and other areas. Likewise, it has also made breakthroughs in the development of molecular imaging. It was recognized that GLP-1R imaging originated from the study of insulinoma and afterwards was expanded in application including islet transplantation, pancreatic β-cell mass measurement, and ATP-dependent potassium channel-related endocrine diseases. Fortunately, GLP-1R molecular imaging has been involved in ischemic cardiomyocytes and neurodegenerative diseases. These signs illustrate the power of GLP-1R molecular imaging in the development of medicine. However, it is still limited to imaging diagnosis research in the current molecular imaging environment. The lack of molecular-targeted therapeutics related report hinders its radiology theranostic. In this article, the current research status, challenges, and emerging opportunities for GLP-1R molecular imaging are discussed in order to open a new path for theranostics and to promote the evolution of molecular medicine.

PMID:37780209 | PMC:PMC10540701 | DOI:10.3389/fmolb.2023.1210347

Identifying target ion channel-related genes to construct a diagnosis model for insulinoma

Fetched: September 30th, 2023, 5:02am GMT by Shuangyang Mo

Front Genet. 2023 Sep 12;14:1181307. doi: 10.3389/fgene.2023.1181307. eCollection 2023.

ABSTRACT

Background: Insulinoma is the most common functional pancreatic neuroendocrine tumor (PNET) with abnormal insulin hypersecretion. The etiopathogenesis of insulinoma remains indefinable. Based on multiple bioinformatics methods and machine learning algorithms, this study proposed exploring the molecular mechanism from ion channel-related genes to establish a genetic diagnosis model for insulinoma. Methods: The mRNA expression profile dataset of GSE73338 was applied to the analysis, which contains 17 insulinoma samples, 63 nonfunctional PNET (NFPNET) samples, and four normal islet samples. Differently expressed ion channel-related genes (DEICRGs) enrichment analyses were performed. We utilized the protein-protein interaction (PPI) analysis and machine learning of LASSO and support vector machine-recursive feature elimination (SVM-RFE) to identify the target genes. Based on these target genes, a nomogram diagnostic model was constructed and verified by a receiver operating characteristic (ROC) curve. Moreover, immune infiltration analysis, single-gene gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were executed. Finally, a drug-gene interaction network was constructed. Results: We identified 29 DEICRGs, and enrichment analyses indicated they were primarily enriched in ion transport, cellular ion homeostasis, pancreatic secretion, and lysosome. Moreover, the PPI network and machine learning recognized three target genes (MCOLN1, ATP6V0E1, and ATP4A). Based on these target genes, we constructed an efficiently predictable diagnosis model for identifying insulinomas with a nomogram and validated it with the ROC curve (AUC = 0.801, 95% CI 0.674-0.898). Then, single-gene GSEA analysis revealed that these target genes had a significantly positive correlation with insulin secretion and lysosome. In contrast, the TGF-beta signaling pathway was negatively associated with them. Furthermore, statistically significant discrepancies in immune infiltration were revealed. Conclusion: We identified three ion channel-related genes and constructed an efficiently predictable diagnosis model to offer a novel approach for diagnosing insulinoma.

PMID:37772258 | PMC:PMC10523017 | DOI:10.3389/fgene.2023.1181307

Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia

Fetched: September 29th, 2023, 5:02am GMT by Rikako Nakajima

Endocrinol Diabetes Metab Case Rep. 2023 Sep 28;2023(3):23-0056. doi: 10.1530/EDM-23-0056. Print 2023 Jul 1.

ABSTRACT

SUMMARY: Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery.

LEARNING POINTS: Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

PMID:37767703 | PMC:PMC10563612 | DOI:10.1530/EDM-23-0056

Permalink for 'Relationship between β-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults'

Relationship between β-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults

Fetched: September 29th, 2023, 5:02am GMT by Tomislav Bulum

Biomedicines. 2023 Sep 18;11(9):2561. doi: 10.3390/biomedicines11092561.

ABSTRACT

AIMS: Our study aimed to investigate the relationship between three autoantibodies and their combination with anthropometric and metabolic components and microvascular complications in patients with latent autoimmune diabetes in adults (LADA).

METHODS: Our study included 189 LADA patients divided into four subgroups according to the autoantibodies present: glutamic acid decarboxylase autoantibodies (GADA) only; zinc transporter-8 autoantibodies (ZnT8A)+GADA; insulinoma-associated-2 autoantibodies (IA-2)+GADA; and ZnT8+IA-2+GADA.

RESULTS: Compared to GADA positivity only, patients with ZnT8+GADA positivity and ZnT8+IA-2+GADA positivity had a shorter diabetes duration and lower body mass index (BMI); patients with ZnT8+GADA positivity were younger and showed an increase in glomerular filtration rate, while those with ZnT8+IA-2+GADA positivity had lower C-peptide and lower insulin resistance measured with HOMA2-IR. In a multiple regression analysis, ZnT8 positivity was associated with lower BMI (p = 0.0024), female sex (p = 0.0005), and shorter duration of disease (p = 0.0034), while IA-2 positivity was associated with lower C-peptide levels (p = 0.0034) and shorter diabetes duration (p = 0.02). No association between antibody positivity and microvascular complications of diabetes, including retinopathy, neuropathy, and microalbuminuria, as well as with variables of glucose control and β-cell function were found.

CONCLUSION: The results of our study suggest that ZnT8 and IA-2 autoantibodies are present in a significant number of LADA patients and associated with clinical and metabolic characteristics resembling classic type 1 diabetes. Due to increased LADA prevalence, earlier identification of patients requiring frequent monitoring with the earlier intensification of insulin therapy might be of special clinical interest.

PMID:37761002 | PMC:PMC10526032 | DOI:10.3390/biomedicines11092561

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response

Fetched: September 28th, 2023, 5:03am GMT by Danhong Lin

Sci Rep. 2023 Sep 27;13(1):16173. doi: 10.1038/s41598-023-43438-7.

ABSTRACT

Lack of efficient insulin secretion from the pancreas can lead to impaired glucose tolerance (IGT), prediabetes, and diabetes. We have previously identified two IGT-associated single nucleotide polymorphisms (SNPs) rs62212118 and rs13052524 located at two overlapping genes: MRPS6 and SLC5A3. In this study, we show that MRPS6 but not SLC5A3 regulates glucose-stimulated insulin secretion (GSIS) in primary human β-cell and a mouse pancreatic insulinoma β-cell line. Data mining and biochemical studies reveal that MRPS6 is positively regulated by the mitochondrial unfolded protein response (UPR^mt), but feedback inhibits UPR^mt. Disruption of such feedback by MRPS6 knockdown causes UPR^mt hyperactivation in high glucose conditions, hence elevated ROS levels, increased apoptosis, and impaired GSIS. Conversely, MRPS6 overexpression reduces UPR^mt, mitigates high glucose-induced ROS levels and apoptosis, and enhances GSIS in an ATF5-dependent manner. Consistently, UPR^mt up-regulation or down-regulation by modulating ATF5 expression is sufficient to decrease or increase GSIS. The negative role of UPR^mt in GSIS is further supported by analysis of public transcriptomic data from murine islets. In all, our studies identify MRPS6 and UPR^mt as novel modulators of GSIS and apoptosis in β-cells, contributing to our understanding of the molecular and cellular mechanisms of IGT, prediabetes, and diabetes.

PMID:37758822 | PMC:PMC10533529 | DOI:10.1038/s41598-023-43438-7

Permalink for 'Newly diagnosed type 1 diabetes mellitus in a human immunodeficiency virus-infected patient with antiretroviral therapy-induced immune reconstitution inflammatory syndrome: a case report'

Newly diagnosed type 1 diabetes mellitus in a human immunodeficiency virus-infected patient with antiretroviral therapy-induced immune reconstitution inflammatory syndrome: a case report

Fetched: September 21st, 2023, 5:02am GMT by None Min-ChunYeh

BMC Infect Dis. 2023 Sep 20;23(1):619. doi: 10.1186/s12879-023-08605-1.

ABSTRACT

BACKGROUND: Diabetes that develops in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) is usually type 2 diabetes mellitus (T2DM); however, autoimmune diabetes, such as type 1 diabetes mellitus (T1DM) can also develop in this population. After treatment with ART, patients might experience clinical deterioration following an increase in the CD4 cell count, which is termed immune reconstitution inflammatory syndrome (IRIS). Here, we describe an HIV-infected patient on ART who developed T1DMat due to IRIS, highlighting the clinical complexity in diagnosis and treatment.

CASE PRESENTATION: A 36-year-old man infected with HIV had a nadir CD4 cell count of 15.53/μL before medication, which increased to 429.09/μL after 9 months of regular ART. The fasting serum glucose at 9 months was between 96 mg/dL and 117 mg/dL. After 11 months of ART, the patient was admitted to hospital for diabetic ketoacidosis (DKA) and Graves' disease (GD). Noninsulin antidiabetics (NIADs) were prescribed following the resolution of DKA. However, poor glycemic control was noted despite well-titrated NIADs. Further investigation demonstrated poor pancreatic beta cell function and elevated anti-glutamic acid decarboxylase (anti-GAD) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) titers. According to the results, he was diagnosed with T1DM and received multiple daily injections(MDI) of insulin. The regimen of MDI was insulin degludec as basal insulin and insulin aspart as prandial insulin. After MDI therapy, his glycemic control was improved.

CONCLUSION: In this case, T1DM was ascribed to IRIS. Although this phenomenon has been demonstrated in previous case reports, further study is necessary to realize the mechanism of this association. Therefore, we emphasize that when HIV-infected patients on ART experience an unstable blood glucose level and abnormal thyroid function, physicians should consider T1DM and GD associated with ART-induced IRIS to reduce the subsequent complications and more serious endocrine dysfunction.

PMID:37730544 | PMC:PMC10512543 | DOI:10.1186/s12879-023-08605-1

A case of repeated severe hypoglycemia caused by accidental ingestion of sulfonylurea in an elderly patient

Fetched: September 21st, 2023, 5:02am GMT by Arina Yamasaki

Nihon Ronen Igakkai Zasshi. 2023;60(3):294-300. doi: 10.3143/geriatrics.60.294.

ABSTRACT

An 81-year-old man was being treated with oral medication for chronic heart failure and epilepsy. He had no history of diabetes, cirrhosis, or gastric surgery. He was admitted to our hospital due to disturbance of consciousness. His blood glucose level was 6 mg/dl, with a relatively high insulin level (14.4 μU/ml). Computed tomography and a 48 h fasting test showed no signs of insulinoma. There were no signs of reactive hypoglycemia, insulin autoimmune syndrome, or adrenal insufficiency. His wife had been taking medication for diabetes, including sulfonylurea. She had dementia, and he managed her medication. Since his medication was found in his wife's medicine box, we considered the possibility that he might have taken sulfonylurea by mistake. We asked his daughter to manage their medicine. However, one month later, he was admitted to our hospital again with severe hypoglycemia. His wife's HbA1c value and estimated glomerular filtration rate were 6.9% and 30 ml/min/1.73 m². We asked his wife's home doctor to stop sulfonylurea prescription, and the hypoglycemia did not recur, with his wife's level of HbA1c remaining stable.Elderly individuals and patients with an impaired renal function are prone to hypoglycemia from sulfonylurea. In elderly households, there is a possibility of accidental ingestion of oral hypoglycemic agents by other family members living with the patient. It is therefore necessary to understand and manage the medications of family members living together. It is also important to avoid prescribing medications with a high risk of hypoglycemia to elderly patients.

PMID:37730332 | DOI:10.3143/geriatrics.60.294

Mechanism and recent updates on insulin-related disorders

Fetched: September 21st, 2023, 5:02am GMT by Shashank Kumar

World J Clin Cases. 2023 Sep 6;11(25):5840-5856. doi: 10.12998/wjcc.v11.i25.5840.

ABSTRACT

Insulin, a small protein with 51 amino acids synthesized by pancreatic β-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

PMID:37727490 | PMC:PMC10506040 | DOI:10.12998/wjcc.v11.i25.5840

Permalink for '18F-labeled PEGylated exendin-4 imaging noninvasively differentiates insulinoma from an accessory spleen: the first case report of [18F]FB(ePEG12)12-exendin-4 positron emission tomography/computed tomography for insulinoma'

18F-labeled PEGylated exendin-4 imaging noninvasively differentiates insulinoma from an accessory spleen: the first case report of [18F]FB(ePEG12)12-exendin-4 positron emission tomography/computed tomography for insulinoma

Fetched: September 19th, 2023, 5:03am GMT by Kentaro Sakaki

Front Endocrinol (Lausanne). 2023 Aug 31;14:1245573. doi: 10.3389/fendo.2023.1245573. eCollection 2023.

ABSTRACT

BACKGROUND: Insulinomas are the most common functioning pancreatic neuroendocrine neoplasms, and these tumors induce hypoglycemia due to hyperinsulinemia. Hypoglycemia caused by insulinomas can cause seizures, coma or death due to the delayed diagnosis. The only curative treatment is surgical resection. To perform curative surgical resection of insulinomas, preoperative localization is crucial. However, localization of insulinomas is often challenging using conventional imaging methods such as computed tomography (CT) and magnetic resonance imaging. Although endoscopic ultrasound (EUS) fine-needle aspiration and selective arterial calcium stimulation test, which can reflect the endocrine character of the tumor, are performed in such cases, these modalities are invasive and require operator-dependent techniques. Additionally, somatostatin receptor (SSTR)-targeted imaging has a relatively low sensitivity for detecting insulinomas due to its low SSTR type 2 expression. Thus, there is an urgent need for developing a noninvasive diagnostic technique which is specific for detecting insulinomas. Consequently, glucagon-like peptide-1 receptor-targeted imaging has recently emerged and gained a wide interest. Recently, we have developed a novel ¹⁸F-labeled exendin-4-based probe conjugated with polyethylene glycol, [¹⁸F]FB(ePEG12)12-exendin-4 (¹⁸F-exendin-4), for positron emission tomography (PET) imaging. Here we report a case of insulinoma in which ¹⁸F-exendin-4 PET/CT noninvasively provided critical information for localization.

CASE DESCRIPTION: This is a case of a 58-year-old male with symptomatic hypoglycemia for 10 years; however, a preoperative diagnosis of insulinoma was not established due to the difficulty in differentiating it from an accessory spleen using conventional imaging. Moreover, the patient requested to avoid invasive diagnostic procedures including EUS. ¹⁸F-exendin-4 PET/CT revealed significant uptakes in the pancreatic tail whereas no apparent uptakes were observed in the spleen; thus, curative laparoscopic enucleation of the pancreatic tail was performed. The diagnosis of insulinoma was confirmed via histopathological examination. This is the first case report of insulinoma diagnosed using ¹⁸F-exendin-4 PET/CT.

CONCLUSION: In this case, PET information led to curative resection through enucleation of the pancreas. ¹⁸F-exendin-4 PET/CT may serve as a useful noninvasive clinical tool for insulinoma localization.

PMID:37720533 | PMC:PMC10501723 | DOI:10.3389/fendo.2023.1245573

Overweight and obesity in children and adolescents with endocrine disorders

Fetched: September 16th, 2023, 5:02am GMT by Renata Pomahacova

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2023 Sep 4. doi: 10.5507/bp.2023.036. Online ahead of print.

ABSTRACT

Obesity has become a serious medical condition where many factors can contribute to excess weight gain. The most common type of childhood obesity is simple obesity, which is due to gene-obesogenic environment interaction. Only a minority are due to pathological causes. Secondary causes of obesity, while less common, include these: genetic syndromes, drug-related obesity, as well as endocrine disorders (hypothyroidism, Cushing's syndrome, growth hormone deficiency, hypogonadism, pseudohypoparathyroidism type Ia, insulinoma, hypothalamic obesity and polycystic ovary syndrome). Given that some conditions may be treatable, physicians must be aware of obesity due to endocrinopathies and distinguish them from simple obesity, and treat them properly. Although rare among children, early detection of the endocrine cause of obesity leads to reduced morbidity and, in some cases, reduced mortality in these individuals. The aim of this review is to summarize the current findings on obesity-related endocrinopathies in children (illustrated by clinical examples), highlighting aspects of pathogenetic mechanisms, genetics, the clinical diagnosis, growth, body mass index and possible therapeutic approaches. Early detection and correction of endocrine obesity is of paramount importance for obese children who could benefit from timely diagnosis and an improved management of obesity as many disturbances related to obesity can be reversed at the early stage, if weight loss is achieved.

PMID:37712247 | DOI:10.5507/bp.2023.036

Insulinoma in Patient With Nonalcoholic Steatohepatitis

Fetched: September 16th, 2023, 5:02am GMT by Daniel Cain

Cureus. 2023 Aug 14;15(8):e43469. doi: 10.7759/cureus.43469. eCollection 2023 Aug.

ABSTRACT

An insulinoma is a rare neuroendocrine tumor characterized by inappropriate secretion of insulin with resultant hypoglycemia and concomitant symptoms. Symptoms include diaphoresis, tremor, palpitations, tachycardia, visual disturbances, weakness, confusion, syncope, seizures, and even coma. Enteropancreatic neoplasms are rare in general but among them, insulinomas are among the more common neuroendocrine tumors though they still have a very low incidence. They can be benign or malignant, however, the latter is exceptionally rare. In the case of malignancy, such spread usually includes metastasis to the liver and surrounding nodes. They can also be sporadic or occur in association with other inherited conditions. Herein, we present a case of insulinoma in a 51-year-old female.

PMID:37711931 | PMC:PMC10499054 | DOI:10.7759/cureus.43469

Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes

Fetched: September 13th, 2023, 5:02am GMT by Jasaman Tojjar

Diabetes Care. 2023 Nov 1;46(11):1993-1996. doi: 10.2337/dc23-0124.

ABSTRACT

OBJECTIVE: To examine sex differences in children with newly diagnosed type 1 diabetes (T1D) with respect to age at diagnosis, presence of autoantibodies (GAD antibody [GADA], insulinoma-associated protein 2 [IA-2A], insulin autoantibody [IAA], and zinc transporter 8 autoantibody), and HLA risk.

RESEARCH DESIGN AND METHODS: A population-based nationwide sample of 3,645 Swedish children at T1D diagnosis was used.

RESULTS: Girls were younger at T1D diagnosis (9.53 vs. 10.23 years; P < 0.001), more likely to be autoantibody-positive (94.7% vs. 92.0%; P = 0.002), more often positive for multiple autoantibodies (P < 0.001), more likely to be positive for GADA (64.9% vs. 49.0%; P < 0.001), and less likely to be positive for IAA (32.3% vs. 33.8%; P = 0.016). Small sex differences in HLA risk were found in children <9 years of age.

CONCLUSIONS: The disease mechanisms leading to T1D may influence the immune system differently in girls and boys.

PMID:37699205 | DOI:10.2337/dc23-0124

INSM1 promotes breast carcinogenesis by regulating C-MYC

Fetched: September 12th, 2023, 5:02am GMT by Yinan Guan

Am J Cancer Res. 2023 Aug 15;13(8):3500-3516. eCollection 2023.

ABSTRACT

Insulinoma-associated protein-1 (INSM1), which is highly expressed in various neuroendocrine tumors, functions as a zinc finger transcription factor capable of regulating the biological behavior of tumor cells. However, its specific role in breast cancer remains unclear. This study aims to investigate the role and mechanism of INSM1 in breast cancer. A total of 158 cohorts were recruited to examine the expression of INSM1 in breast cancer tissues and their corresponding adjacent normal tissues using immunohistochemistry. Follow-up data, along with clinical and pathological information, were collected to analyze the correlation between INSM1 expression and survival outcomes in breast cancer patients. Additionally, we investigated the impact of INSM1 on breast cancer cell proliferation, migration, and aggregation. To further explore the regulatory effect of INSM1 knockdown on breast cancer tumor growth, we utilized a xenograft mouse model. The results revealed that INSM1 was significantly overexpressed in breast cancer patients and correlated with prognosis. Knockdown of INSM1 notably impaired the malignant biological effects of breast cancer cells and inhibited the growth of xenograft tumors in nude mice. Importantly, our data also suggests an interaction between INSM1 and S-phase kinase-associated protein 2 (SKP2), which in turn regulates C-MYC, thereby affecting the p-ERK pathway. Our study provides the first evidence demonstrating the contribution of INSM1 to tumor formation and growth in breast cancer. Furthermore, we found that INSM1 positively regulates C-MYC and the p-ERK pathway by interacting with SKP2 during breast cancer development. Collectively, these findings highlight INSM1 as a promising target for breast cancer treatment.

PMID:37693125 | PMC:PMC10492136

Thymoma in multiple endocrine neoplasia type 1: a case report and systematic review

Fetched: September 6th, 2023, 5:02am GMT by Yuting Gao

Endocrine. 2023 Nov;82(2):442-449. doi: 10.1007/s12020-023-03440-5. Epub 2023 Sep 5.

ABSTRACT

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature.

METHODS: A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2 × 1.5 cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783 + 1G > A in the MEN1 gene was identified. We further searched PubMed and EMBASE for thymoma in association with MEN1.

RESULTS: A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted.

CONCLUSIONS: Besides carcinoid, other tumors, including thymoma, need to be identified for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.

PMID:37668926 | DOI:10.1007/s12020-023-03440-5

Reducing kidney uptake of radiolabelled exendin-4 using variants of the renally cleavable linker MVK

Fetched: September 5th, 2023, 5:02am GMT by Belinda Trachsel

EJNMMI Radiopharm Chem. 2023 Sep 4;8(1):21. doi: 10.1186/s41181-023-00206-2.

ABSTRACT

BACKGROUND: Peptidic radiotracers are preferentially excreted through the kidneys, which often results in high persistent renal retention of radioactivity, limiting or even preventing therapeutic clinical translation of these radiotracers. Exendin-4, which targets the glucagon-like-peptide 1 receptor (GLP-1R) overexpressed in insulinomas and in congenital hyperinsulinism, is an example thereof. The use of the tripeptide MVK, which is readily cleaved between methionine and valine by neprilysin at the renal brush border membrane, already showed promising results in reducing kidney uptake as reported in the literature. Based on our previous findings we were interested how linker variants with multiple copies of the MV-motive influence renal washout of radiolabelled exendin-4.

RESULTS: Three exendin-4 derivatives, carrying either one MVK, a MV-MVK or a MVK-MVK linker were synthesized and compared to a reference compound lacking a cleavable linker. In vivo results of a biodistribution in GLP-1R overexpressing tumour bearing mice at 24 h post-injection demonstrated a significant reduction (at least 57%) of renal retention of all ¹¹¹In-labeled exendin-4 compounds equipped with a cleavable linker compared to the reference compound. While the insertion of the single linker MVK led to a reduction in kidney uptake of 70%, the dual approach with the linker MV-MVK slightly, but not significantly enhanced this effect, with 77% reduction in kidney uptake compared to the reference. In vitro IC50 and cell uptake studies were conducted and demonstrated that though the cleavable linkers negatively influenced the affinity towards the GLP-1R, cell uptake remained largely unaffected, except for the MV-MVK cleavable linker conjugate, which displayed lower cell uptake than the other compounds. Importantly, the tumour uptake in the biodistribution study was not significantly affected with 2.9, 2.5, 3.2 and 1.5% iA/g for radiolabelled Ex4, MVK-Ex4, MV-MVK-Ex4 and MVK-MVK-Ex4, respectively.

CONCLUSION: Cleavable linkers are highly efficient in reducing the radioactivity burden in the kidney. Though the dual linker approach using the instillation of MV-MVK or MVK-MVK between exendin-4 and the radiometal chelator did not significantly outperform the single cleavable linker MVK, further structural optimization or the combination of different cleavable linkers could be a stepping stone in reducing radiation-induced nephrotoxicity.

PMID:37665477 | PMC:PMC10477158 | DOI:10.1186/s41181-023-00206-2

$Permalink for 'Automated production of [68Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module'$

Automated production of [68Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module

Fetched: August 28th, 2023, 5:02am GMT by Martin Kraihammer

Nucl Med Biol. 2023 Sep-Oct;124-125:108381. doi: 10.1016/j.nucmedbio.2023.108381. Epub 2023 Aug 18.

ABSTRACT

BACKGROUND: PET/CT imaging of glucagon-like peptide receptor 1 has recently filled a gap in reliably diagnosing insulinoma through non-invasive means. ⁶⁸Ga-labelled derivatives of exendin-4 show high sensitivity as well as sufficient serum stability to enable routine clinical application. Here, we provide data for automated production of [⁶⁸Ga][Nle¹⁴,Lys⁴⁰(Ahx-DOTA-Ga)NH2]exendin-4 ([⁶⁸Ga]Ga-DOTA-exendin-4) on a cassette based synthesis module (Modular-Lab PharmTracer, Eckert & Ziegler) using commercially available cassettes in combination with an approved ⁶⁸Ge/⁶⁸Ga generator (GalliaPharm, Eckert & Ziegler). This setup ensured high reproducibility as well as low radiation burden for the production team. Quality control including determination of radiochemical purity was performed by RP-HPLC using a water/0.1 % TFA/acetonitrile gradient on a C18 column. A modified TLC system with ammonium acetate & methanol as mobile phase and a novel limit test for determination of polysorbate 80 content in the final formulation are also described in this study.

MAIN FINDINGS: Reliable yields as well as high molar activity for patient use were only achieved using a fractionated elution approach. Batch data showed radiochemical purity of >93 % as determined by RP-HPLC and TLC as well as good stability over 2 h post production. Testing for polysorbate 80 confirmed a concentration <1 mg/mL in the final product solution. Specifications for routine production were established based on existing Pharmacopeia monographs for other radiopharmaceuticals and were validated with 5 master batches.

CONCLUSION: The described synthesis method enables reproducible, automated in-house production of [⁶⁸Ga]Ga-DOTA-exendin-4 for routine clinical application.

PMID:37634398 | DOI:10.1016/j.nucmedbio.2023.108381

Permalink for 'Dynamic electro-clinical changes corresponding to immediate recovery after glucose administration from insulinoma-induced hypoglycemia: report of two cases'

Dynamic electro-clinical changes corresponding to immediate recovery after glucose administration from insulinoma-induced hypoglycemia: report of two cases

Fetched: August 28th, 2023, 5:02am GMT by Kazutoshi Konomatsu

Epileptic Disord. 2023 Aug 26. doi: 10.1002/epd2.20155. Online ahead of print.

NO ABSTRACT

PMID:37632394 | DOI:10.1002/epd2.20155

Diagnosis and Surgical Management of Insulinomas-A 23-Year Single-Center Experience

Fetched: August 27th, 2023, 5:02am GMT by David Hoskovec

Medicina (Kaunas). 2023 Aug 4;59(8):1423. doi: 10.3390/medicina59081423.

ABSTRACT

Background and Objectives: Insulinoma is a rare tumor of the Langerhans islets of the pancreas. It produces insulin and causes severe hypoglycemia with neuroglycopenic symptoms. The incidence is low, at about 1-2 per 1 million inhabitants per year. The diagnosis is based on the presence of Whipple's triad and the result of a fasting test. Surgery is the treatment of choice. Objectives: A retrospective observational study of patients operated on for insulinoma in our hospital focused on the diagnosis, the type of surgery, and complications. Materials and Methods: We retrospectively reviewed patients operated on due to insulinoma. There were 116 surgeries between 2000 and 2022. There were 79 females and 37 males in this group. A fasting test and a CT examination were performed on all the patients. Results: The average duration of the fasting test was 18 h. Insulinoma was found in the body and tail of the pancreas in more than half of the patients. Enucleation was the most frequent type of surgery. Complications that were Clavien Dindo grade III or more occurred in 18% of the patients. The most frequent complications were abscesses and pancreatic fistula. Five patients had malignant insulinoma. Conclusions: Surgery is the treatment of choice in the case of insulinomas. The enucleation of the tumor is a sufficient treatment for benign insulinomas, which are not in contact with the main pancreatic duct. Due to the low incidence of the condition, the centralization of patients is recommended.

PMID:37629713 | PMC:PMC10456644 | DOI:10.3390/medicina59081423

Insulinoma Associated with MEN1 Syndrome: A Case of Persistent Hypoglycemia in School-aged Child

Fetched: August 26th, 2023, 5:02am GMT by Rodrigo Lemus-Zepeda

J Clin Res Pediatr Endocrinol. 2023 Aug 25. doi: 10.4274/jcrpe.galenos.2023.2023-3-10. Online ahead of print.

ABSTRACT

Insulinoma is a rare cause of non-ketotic hypoglycemia both in adults and in children. Pediatric patients account for approximately 5% of all cases, mostly due to isolated benign lesions, but it can also be part of a multiple endocrine neoplasia type 1 syndrome (MEN1). We report the case of a patient with multiple hospitalizations related to hypoglycemia and neuroglycopenia symptoms, with multiple studies demonstrating the presence of an insulinoma as part of the spectrum of MEN1 syndrome. The primary significance of our report is to underscore that insulinoma can present as the initial manifestation of MEN1 syndrome in 10% of pediatric patients. Furthermore, we describe a likely pathogenic variant in the MEN1 gene not previously reported in the literature. Our report highlights the importance of the convergence of clinical, biochemical and molecular investigations in establishing a precise diagnosis, prognosis, and appropriate follow-up for pediatric patients with hypoglycemia.

PMID:37621212 | DOI:10.4274/jcrpe.galenos.2023.2023-3-10

$Permalink for 'Anti-Insulin Receptor Antibody for Malignant Insulinoma and Refractory Hypoglycemia'$

Anti-Insulin Receptor Antibody for Malignant Insulinoma and Refractory Hypoglycemia

Fetched: August 24th, 2023, 5:02am GMT by Soravis Osataphan

N Engl J Med. 2023 Aug 24;389(8):767-769. doi: 10.1056/NEJMc2307576.

NO ABSTRACT

PMID:37611129 | PMC:PMC10506502 | DOI:10.1056/NEJMc2307576

Permalink for 'High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin'

High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin

Fetched: August 24th, 2023, 5:02am GMT by Anne-Sophie Litmeyer

J Pathol Clin Res. 2023 Nov;9(6):498-509. doi: 10.1002/cjp2.339. Epub 2023 Aug 22.

ABSTRACT

Complementary to synaptophysin and chromogranin A, insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrine carcinomas (MANECs/NECs), we examined INSM1 in a large cohort of conventional CRCs and MANECs/NECs. In conventional CRC, we put a special focus on conventional CRC with diffuse expression of synaptophysin, which carry the risk of being misinterpreted as a MANEC or a NEC. We investigated INSM1 according to the immunoreactive score in our main cohort of 1,033 conventional CRCs and 21 MANECs/NECs in comparison to the expression of synaptophysin and chromogranin A and correlated the results with clinicopathological parameters and patient survival. All MANECs/NECs expressed INSM1, usually showing high or moderate expression (57% high, 34% moderate, and 9% low), which distinguished them from conventional CRCs, which were usually INSM1 negative or low, even if they diffusely expressed synaptophysin. High expression of INSM1 was not observed in conventional CRCs. Chromogranin A was negative/low in most conventional CRCs (99%), but also in most MANECs/NECs (66%). Comparable results were observed in our independent validation cohorts of conventional CRC (n = 274) and MANEC/NEC (n = 19). Similar to synaptophysin, INSM1 expression had no prognostic relevance in conventional CRCs, while true MANEC/NEC showed a highly impaired survival in univariate and multivariate analyses (e.g. disease-specific survival: p < 0.001). MANECs/NECs are a highly aggressive variant of colorectal cancer, which must be reliably identified. High expression of INSM1 distinguishes MANEC/NEC from conventional CRCs with diffuse expression of the standard neuroendocrine marker synaptophysin, which do not share the same dismal prognosis. Therefore, high INSM1 expression is a highly specific/sensitive marker that is supportive for the diagnosis of true colorectal MANEC/NEC.

PMID:37608427 | PMC:PMC10556265 | DOI:10.1002/cjp2.339

Permalink for 'A posteriori diagnosis of DRESS syndrome induced by diazoxide in a patient with an insulinoma: a case report and review of the literature'

A posteriori diagnosis of DRESS syndrome induced by diazoxide in a patient with an insulinoma: a case report and review of the literature

Fetched: August 22nd, 2023, 5:02am GMT by Najoua Lassoued

Front Med (Lausanne). 2023 Aug 4;10:1196041. doi: 10.3389/fmed.2023.1196041. eCollection 2023.

ABSTRACT

The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome can be potentially life-threatening. The diagnosis is sometimes difficult since the clinical manifestations may be incomplete or non-specific. Insulinoma is a rare functioning neuroendocrine tumor (NET) of the pancreas. Medical therapy may be needed when surgery is contraindicated, delayed or refused. Diazoxide is widely used to control hypoglycemia in patients with insulinoma. We report a clinical case of an insulinoma in a 85-year-old patient treated with diazoxide with a fatal outcome due to a delayed diagnosis of a DRESS syndrome. This is the first case of DRESS syndrome reported after using diazoxide for insulinoma treatment in our knowledge.

PMID:37601782 | PMC:PMC10436324 | DOI:10.3389/fmed.2023.1196041

Insulinoma in pediatric tuberous sclerosis complex: a case report

Fetched: August 22nd, 2023, 5:02am GMT by Katia Librandi

Front Pediatr. 2023 Jul 19;11:1216201. doi: 10.3389/fped.2023.1216201. eCollection 2023.

ABSTRACT

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare multisystemic disorder. This genetically determined disease is characterized by highly variable clinical expression, including epilepsy as a common feature. Seizures can also occur as a manifestation of symptomatic hypoglycemia. The latter could be caused by an insulinoma, whose association to TSC has already been debated. In TSC-associated tumors, dysregulation of the mTOR pathway is believed to be present, leading to significant impacts on cellular metabolism, growht, and proliferation. To date, the association between TSC and insulinoma has been reported in 11 adults. Here, we present the first case of a pediatric patient with TSC diagnosed with an insulinoma and review the existing literature on this topic.

CASE PRESENTATION: A 11-year-old female with TSC presented with seizures unresponsive to standard therapy. Further investigation revealed that these seizures were caused by hypoglycemia. Subsequent evaluation led to the diagnosis of a pancreatic insulinoma, which was surgically removed. Following the procedure, the patient was free from seizures.

CONCLUSIONS: In individuals with TSC, the recurrence of epileptiform episodes throughout their lifetime, especially if previously well controlled with antiepileptic therapy, should raise suspicion for hypoglycemic events. These events may potentially be associated with the presence of an insulinoma. Further research and increased awareness are necessary to gain a better understanding of the association between TSC and insulinomas, and to guide clinical management strategies.

PMID:37601129 | PMC:PMC10436085 | DOI:10.3389/fped.2023.1216201

Insulinoma

Fetched: August 19th, 2023, 5:01am GMT by Fenghao Zhuo

2023 Jun 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–.

ABSTRACT

Insulinoma is a type of functional neuroendocrine tumor (NET) that manifests with hypoglycemia caused by inappropriately high insulin secretion. It more commonly presents as a solitary benign tumor, but it can sometimes be associated with multiple endocrine neoplasia type 1 (MEN1). Patients with insulinoma have hypoglycemic episodes, more characteristically as fasting hypoglycemia. Insulinoma is usually diagnosed by biochemical testing when there is high clinical suspicion. Surgical resection is the preferred treatment choice. Localization with imaging studies is fundamental to characterize the tumor better before surgical resection. Other treatment options are also available depending on the stage and grade of the tumor.

PMID:31335019 | Bookshelf:NBK544299

Unveiling nanoscale optical signatures of cytokine-induced β-cell dysfunction

Fetched: August 17th, 2023, 5:02am GMT by Licia Anna Pugliese

Sci Rep. 2023 Aug 16;13(1):13342. doi: 10.1038/s41598-023-40272-9.

ABSTRACT

Pro-inflammatory cytokines contribute to β-cell failure in both Type-1 and Type-2 Diabetes. Data collected so far allowed to dissect the genomic, transcriptomic, proteomic and biochemical landscape underlying cytokine-induced β-cell progression through dysfunction. Yet, no report thus far complemented such molecular information with the direct optical nanoscopy of the β-cell subcellular environment. Here we tackle this issue in Insulinoma 1E (INS-1E) β-cells by label-free fluorescence lifetime imaging microscopy (FLIM) and fluorescence-based super resolution imaging by expansion microscopy (ExM). It is found that 24-h exposure to IL-1β and IFN-γ is associated with a neat modification of the FLIM signature of cell autofluorescence due to the increase of either enzyme-bound NAD(P)H molecules and of oxidized lipid species. At the same time, ExM-based direct imaging unveils neat alteration of mitochondrial morphology (i.e. ~ 80% increase of mitochondrial circularity), marked degranulation (i.e. ~ 40% loss of insulin granules, with mis-localization of the surviving pool), appearance of F-actin-positive membrane blebs and an hitherto unknown extensive fragmentation of the microtubules network (e.g. ~ 37% reduction in the number of branches). Reported observations provide an optical-microscopy framework to interpret the amount of molecular information collected so far on β-cell dysfunction and pave the way to future ex-vivo and in-vivo investigations.

PMID:37587148 | PMC:PMC10432522 | DOI:10.1038/s41598-023-40272-9

European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes

Fetched: August 15th, 2023, 5:02am GMT by Johannes Hofland

J Neuroendocrinol. 2023 Aug;35(8):e13318. doi: 10.1111/jne.13318. Epub 2023 Aug 14.

ABSTRACT

This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET-associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work-up as well as therapeutic management of the individual hormonal syndromes in well-differentiated, grade 1-3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.

PMID:37578384 | DOI:10.1111/jne.13318

Editorial: Neuroendocrine tumors: the road to precision medicine

Fetched: August 12th, 2023, 5:01am GMT by Anna La Salvia

Front Endocrinol (Lausanne). 2023 Jul 26;14:1253319. doi: 10.3389/fendo.2023.1253319. eCollection 2023.

NO ABSTRACT

PMID:37564989 | PMC:PMC10411878 | DOI:10.3389/fendo.2023.1253319

Unmasked insulinoma occasioned by severe hypoglycemic coma immediately postpartum: a case report

Fetched: August 11th, 2023, 5:02am GMT by Kiyoshi Matsumoto

BMC Endocr Disord. 2023 Aug 10;23(1):168. doi: 10.1186/s12902-023-01415-1.

ABSTRACT

BACKGROUND: Insulinoma in women during pregnancy and postpartum is very rare; approximately 65% of cases are diagnosed early in pregnancy and ~ 35% immediately after delivery, few being found in middle or late pregnancy, likely due to increased insulin resistance seen after early-stage pregnancy. We successfully treated a case of insulinoma in which severe hypoglycemic coma immediately after delivery occasioned detailed investigation and diagnosis.

CASE PRESENTATION: Our patient experienced hypoglycemic coma in the 3^rd month of pregnancy (initially considered due to her hyperemesis gravidarum) that improved spontaneously during the gestational period. No abnormalities of plasma glucose or body weight were found in regular checkups during her pregnancy; however, recurrence of hypoglycemic coma after delivery led us to suspect insulinoma. While contrast enhanced computer tomography and endoscopic ultrasonography (EUS) initially failed to detect a tumor in the pancreas, selective arterial calcium stimulation test revealed an insulin-secreting tumor localized in the pancreatic body. She then underwent spleen-preserving distal pancreatectomy; a 10-mm tumor positive for chromogranin A, synaptophysin and insulin was identified.

CONCLUSIONS: Although pregnancy can mask insulinoma-associated symptoms and make diagnosis challenging, hypoglycemic episodes during early pregnancy, which were observed in this case, are suggestive of insulinoma. Importantly, in this case, accurate preoperative localization of the tumor enabled prompt curative surgery after delivery. Thus, clinical vigilance for the occurrence of insulinoma and its localization is appropriate for pregnant women suffering severe hypoglycemia.

PMID:37563593 | PMC:PMC10413590 | DOI:10.1186/s12902-023-01415-1

Imatinib prevents dexamethasone-induced pancreatic β-cell apoptosis via decreased TRAIL and DR5

Fetched: August 10th, 2023, 5:02am GMT by Suchanoot Kutpruek

J Cell Biochem. 2023 Sep;124(9):1309-1323. doi: 10.1002/jcb.30450. Epub 2023 Aug 9.

ABSTRACT

Prolonged administration of dexamethasone, a potent anti-inflammatory drug, can lead to steroid-induced diabetes. Imatinib, a medication commonly prescribed for chronic myeloid leukemia (CML), has been shown to improve diabetes in CML patients. Our recent study demonstrated that dexamethasone induces pancreatic β-cell apoptosis by upregulating the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 5 (DR5). We hypothesized that imatinib may protect against dexamethasone-induced pancreatic β-cell apoptosis by reducing the expression of TRAIL and DR5, thereby favorably modulating downstream effectors in apoptotic pathways. We test this hypothesis by assessing the effects of imatinib on dexamethasone-induced apoptosis in rat insulinoma cell line cells. As anticipated, dexamethasone treatment led to increased TRAIL and DR5 expression, as well as an elevation in superoxide production. Conversely, expression of the TRAIL decoy receptor (DcR1) was decreased. Moreover, key effectors in the extrinsic and intrinsic apoptosis pathways, such as B-cell lymphoma 2 (BCL-2) associated X (BAX), nuclear factor kappa B (NF-κb), P73, caspase 8, and caspase 9, were upregulated, while the antiapoptotic protein BCL-2 was downregulated. Interestingly and importantly, imatinib at a concentration of 10 µM reversed the effect of dexamethasone on TRAIL, DR5, DcR1, superoxide production, BAX, BCL-2, NF-κB, P73, caspase 3, caspase 8, and caspase 9. Similar effects of imatinib on dexamethasone-induced TRAIL and DR5 expression were also observed in isolated mouse islets. Taken together, our findings suggest that imatinib protects against dexamethasone-induced pancreatic β-cell apoptosis by reducing TRAIL and DR5 expression and modulating downstream effectors in the extrinsic and intrinsic apoptosis pathways.

PMID:37555250 | DOI:10.1002/jcb.30450

Von Hippel-Lindau Disease (VHL): Characteristic Lesions with Classic Imaging Findings

Fetched: August 10th, 2023, 5:02am GMT by Suryansh Bajaj

J Kidney Cancer VHL. 2023 Aug 3;10(3):23-31. doi: 10.15586/jkcvhl.v10i3.293. eCollection 2023.

ABSTRACT

Von Hippel-Lindau disease (VHL) is a multisystem cancer syndrome caused by the inactivation of the VHL tumor suppressor gene and involves various organ systems including the central nervous system (CNS), endocrine system, and the kidneys. Tumors seen in patients with VHL disease can be benign or malignant and are usually multifocal, bilateral, and hypervascular in nature. As most lesions associated with VHL are asymptomatic initially, early diagnosis and the institution of an evidence-based surveillance protocol are of paramount importance. Screening, surveillance, and genetic counseling are key aspects in the management of patients diagnosed with VHL disease and often require a multidisciplinary approach and referral to specialized centers. This article will discuss the characteristic lesions seen with VHL disease, their diagnosis, screening protocols and management strategies, as well as an illustrative case to demonstrate the natural progression of the disease with classic imaging findings.

PMID:37555195 | PMC:PMC10404985 | DOI:10.15586/jkcvhl.v10i3.293

Preoperative detection of functional somatostatin receptors in a patient with an insulinoma

Fetched: August 8th, 2023, 5:02am GMT by Kohei Oguni

Clin Case Rep. 2023 Aug 2;11(8):e7771. doi: 10.1002/ccr3.7771. eCollection 2023 Aug.

ABSTRACT

Octreotide is used in patients with insulinomas to treat hypoglycemia, and somatostatin receptor (SSTR) 2 expression is important for its efficacy. We report a case of insulinoma in a 50-year-old woman that responded to an octreotide test, showed accumulation in somatostatin scintigraphy, and was positive for SSTR2A on immunostaining.

PMID:37546161 | PMC:PMC10397476 | DOI:10.1002/ccr3.7771

Pancreatic insulinoma: Diagnosis and treatment of a rare tumour with misleading symptoms - A case report

Fetched: August 4th, 2023, 5:02am GMT by Emmanuel Agbozo

Int J Surg Case Rep. 2023 Aug;109:108603. doi: 10.1016/j.ijscr.2023.108603. Epub 2023 Aug 1.

ABSTRACT

INTRODUCTION: Insulinomas are an uncommon occurrence, with an annual incidence of approximately 4 per million. These functional pancreatic neuroendocrine tumours can present with a myriad of nonspecific symptoms leading to frequent misdiagnoses.

PRESENTATION OF CASE: In this case report is presented a 55-year-old man who was misdiagnosed and managed for a seizure disorder with escalating antiepileptic treatments for 11 months. A thorough history after an attack was the main tool in solving the mystery of his refractory seizures, leading to the discovery of a pancreatic insulinoma. Biochemical tests revealed fasting hypoglycaemia and a relative hyperinsulinemia, and a distal pancreatic lesion measuring approximately 1.8 cm × 1.3 cm was detected on CT, MRI and endoscopic ultrasound. Successful laparoscopic pancreatic left resection led to complete resolution of symptoms and restoration of quality of life to pre-illness levels.

DISCUSSION AND CONCLUSION: Insulinomas have historically been difficult to diagnose because their symptoms mimic neurologic and psychiatric conditions. Patterns of symptom occurrence obtained from a carefully-taken history is the single most important tool in assessing patients with insulinomas, who usually present with unusual and refractory neuropsychiatric conditions.

PMID:37536098 | PMC:PMC10412831 | DOI:10.1016/j.ijscr.2023.108603

Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm

Fetched: August 4th, 2023, 5:02am GMT by Z Cao

Beijing Da Xue Xue Bao Yi Xue Ban. 2023 Aug 18;55(4):575-581. doi: 10.19723/j.issn.1671-167X.2023.04.001.

ABSTRACT

OBJECTIVE: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN).

METHODS: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, β-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, β-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN.

RESULTS: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G1 and 2 cases of G3 types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. β-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. β-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05).

CONCLUSION: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

PMID:37534634 | PMC:PMC10398779 | DOI:10.19723/j.issn.1671-167X.2023.04.001

Cutaneous Neuroendocrine Mucinous Carcinomas Are Low-grade But May Be Associated With Other Cancers

Fetched: August 3rd, 2023, 5:02am GMT by Kathryn E Adkins

Am J Surg Pathol. 2023 Oct 1;47(10):1186-1191. doi: 10.1097/PAS.0000000000002107. Epub 2023 Aug 3.

ABSTRACT

Primary cutaneous mucinous sweat gland carcinoma is said to be prognostically stratifiable by neuroendocrine differentiation, however, this assertion is based on historical data and older staining techniques. We aimed to evaluate the percentage of mucinous and nonmucinous adnexal tumors expressing the newer, more sensitive neuroendocrine marker insulinoma-associated protein 1 (INSM1), and to assess clinicopathologic features in patients cohorted by this phenotype. Of 12 available adnexal/cutaneous adenocarcinomas, 9 were mucinous, 3/9 of which were INSM1-negative, and 2/3 with nodal metastases. Of 3 nonmucinous cases, all were INSM1-negative, 1/3 with nodal metastasis, and 2/3 with lymphovascular invasion. In contrast, of 6 mucinous INSM1-positive cases, no cases had LVI or metastasis, however, 3 patients died during follow-up, 2 from breast or urothelial cancer. A fourth patient developed breast carcinoma. INSM1-positive tumors, from cheek (3), scalp (2), and chin (1) were estrogen receptor and progesterone receptor positive. No cases of apocrine adenoma or hidrocystoma, basal cell, or sebaceous carcinoma labeled with INSM1. While most primary cutaneous mucinous carcinomas are of the neuroendocrine type, our study confirms the presence of occasional non-neuroendocrine mucinous carcinomas. We validate the association of such tumors and nonmucinous non-neuroendocrine adnexal carcinoma with intermediate-grade behavior, including lymph node metastases, but not death. Conversely, neuroendocrine expressing primary cutaneous mucinous carcinoma may represent the well-differentiated neuroendocrine neoplasm/neuroendocrine tumor primary to skin, with low-grade behavior, but attendant risk of germline susceptibility to other aggressive extracutaneous tumors. Routine assessment of cutaneous adnexal carcinoma with INSM1 and longer term follow-up and cancer screening of patients with positive staining is recommended.

PMID:37530225 | PMC:PMC10529824 | DOI:10.1097/PAS.0000000000002107

Automated High-Throughput, High-Content 3D Imaging of Intact Pancreatic Islets

Fetched: August 2nd, 2023, 5:02am GMT by Sean M McCarty

SLAS Discov. 2023 Jul 31:S2472-5552(23)00052-7. doi: 10.1016/j.slasd.2023.07.003. Online ahead of print.

ABSTRACT

Diabetes poses a global health crisis affecting individuals across age groups and backgrounds, with a prevalence estimate of 700 million people worldwide by 2045. Current therapeutic strategies primarily rely on insulin therapy or hypoglycemic agents, which fail to address the root cause of the disease - the loss of pancreatic insulin-producing beta-cells. Therefore, bioassays that recapitulate intact islets are needed to enable drug discovery for beta-cell replenishment, protection from beta-cell loss, and islet-cell interactions. Standard cancer insulinoma beta-cell lines MIN6 and INS-1 have been used to interrogate beta-cell metabolic pathways and function but are not suitable for studying proliferative effects. Screening using primary human/rodent intact islets offers a higher level of physiological relevance to enhance diabetes drug discovery and development. However, the 3-dimensionality of intact islets have presented challenges in developing robust, high-throughput assays to detect beta-cell proliferative effects. Established methods rely on either dissociated islet cells plated in 2D monolayer cultures for imaging or reconstituted pseudo-islets formed in round bottom plates to achieve homogeneity. These approaches have significant limitations due to the islet cell dispersion process. To address these limitations, we have developed a robust, intact ex vivo pancreatic islet bioassay in 384-well format that is capable of detecting diabetes-relevant endpoints including beta-cell proliferation, chemoprotection, and islet spatial morphometrics.

PMID:37527729 | DOI:10.1016/j.slasd.2023.07.003

Endocrine disorders associated with obesity

Fetched: August 1st, 2023, 5:02am GMT by Hyeong-Kyu Park

Best Pract Res Clin Obstet Gynaecol. 2023 Aug;90:102394. doi: 10.1016/j.bpobgyn.2023.102394. Epub 2023 Jul 20.

ABSTRACT

Several endocrine disorders, including diabetes, insulinoma, Cushing syndrome, hypothyroidism, polycystic ovarian syndrome, and growth hormone deficiency, are associated with obesity. The mechanisms underlying the development of obesity vary according to the abnormalities of endocrine function. The primary actions of insulin, glucocorticoids (GCs), thyroid hormone, and growth hormone are associated with energy metabolism in the liver, muscle, adipose tissue, and other tissues. This chapter describes the pathogenesis of obesity and metabolic dysfunction associated with excess insulin or GCs and the deficiency of thyroid hormone or growth hormone.

PMID:37523934 | DOI:10.1016/j.bpobgyn.2023.102394

Permalink for 'One hundred years after the discovery of insulin and glucagon: the history of tumors and hyperplasias that hypersecrete these hormones'

One hundred years after the discovery of insulin and glucagon: the history of tumors and hyperplasias that hypersecrete these hormones

Fetched: July 29th, 2023, 5:01am GMT by Wouter W de Herder

Endocr Relat Cancer. 2023 Jul 28;30(9):e230046. doi: 10.1530/ERC-23-0046. Print 2023 Sep 1.

ABSTRACT

One century ago, in 1922, Frederick G Banting, Charles H Best, James B Collip and John J R Macleod first published their experiments resulting in the isolation of a hypoglycemic factor, named insulin, from a solution extract from a dog's pancreas. One year later, in 1923, a hyperglycemic factor named glucagon was isolated by Charles P Kimball and John R Murlin. In the following years, it could be demonstrated that pancreatic islet alpha- and beta-cell neoplasms and hyperplasias could inappropriately secrete excessive amounts of these two hormones. This review is a sequel to the discovery of insulin and glucagon and introduces the history of this fascinating group of neuroendocrine neoplasms and hyperplasias of the pancreas.

PMID:37310813 | DOI:10.1530/ERC-23-0046

Retracted: Effect of HIV-1 Protease Inhibitor on IL-18 and IL-1β in Rats with Insulinoma

Fetched: July 29th, 2023, 5:01am GMT by Disease Markers

Dis Markers. 2023 Jul 19;2023:9876090. doi: 10.1155/2023/9876090. eCollection 2023.

ABSTRACT

[This retracts the article DOI: 10.1155/2022/1868749.].

PMID:37502600 | PMC:PMC10371675 | DOI:10.1155/2023/9876090

Permalink for 'Confirmed and presumed canine insulinomas and their presumed metastases are most conspicuous in the late arterial phase in a triple arterial phase CT protocol'

Confirmed and presumed canine insulinomas and their presumed metastases are most conspicuous in the late arterial phase in a triple arterial phase CT protocol

Fetched: July 28th, 2023, 5:02am GMT by Adrianna Skarbek

Vet Radiol Ultrasound. 2023 Sep;64(5):834-843. doi: 10.1111/vru.13278. Epub 2023 Jul 26.

ABSTRACT

Arterial enhancement is the commonly described characteristic of canine insulinomas in contrast-enhanced computed tomography (CECT). However, this finding is also reported as inconsistent. The main aim of this single-center retrospective observational study was to describe the contrast enhancement (CE) pattern of canine presumed and confirmed insulinomas and presumed metastases in three consecutive (early, mid, and late) arterial phases. Included dogs had a medical-record-based clinical or cytological/histopathological diagnosis of insulinoma and quadruple-phase CECT. The arterial phases were identified according to published literature. The arterial enhancement of confirmed and presumed lesions was assessed using a visual grading score. Twelve dogs with a total of 17 pancreatic nodules were analyzed. Three dogs had multiple pancreatic nodules and nine had solitary findings. Four insulinomas were histopathologically confirmed. Late arterial phase (LAP) images demonstrated the largest number of pancreatic nodules reaching the highest enhancement scores (n = 13, 76%). All analyzed dogs had CT evidence of arterially enhancing nodules in the liver (n = 12), seven in the hepatic, splenic, or colic lymph nodes, and three in the spleen. Three out of five sampled livers and three lymph nodes were metastatic. All sampled spleens were benign. Avid arterial enhancement was the most dominant feature of canine presumed and confirmed insulinomas and presumed metastases in quadruple-phase CECT. The highest enhancement scores were observed primarily in LAP, followed by MAP. Authors, therefore, recommend including LAP in the standard CT protocol for dogs with suspected pancreatic insulinomas.

PMID:37496364 | DOI:10.1111/vru.13278

Permalink for 'Pancreatic CT perfusion: quantitative meta-analysis of disease discrimination, protocol development, and effect of CT parameters'

Pancreatic CT perfusion: quantitative meta-analysis of disease discrimination, protocol development, and effect of CT parameters

Fetched: July 22nd, 2023, 5:02am GMT by Stephan Skornitzke

Insights Imaging. 2023 Jul 21;14(1):132. doi: 10.1186/s13244-023-01471-0.

ABSTRACT

BACKGROUND: This study provides a quantitative meta-analysis of pancreatic CT perfusion studies, investigating choice of study parameters, ability for quantitative discrimination of pancreatic diseases, and influence of acquisition and reconstruction parameters on reported results.

METHODS: Based on a PubMed search with key terms 'pancreas' or 'pancreatic,' 'dynamic' or 'perfusion,' and 'computed tomography' or 'CT,' 491 articles published between 1982 and 2020 were screened for inclusion in the study. Inclusion criteria were: reported original data, human subjects, five or more datasets, measurements of pancreas or pancreatic pathologies, and reported quantitative perfusion parameters. Study parameters and reported quantitative measurements were extracted, and heterogeneity of study parameters and trends over time are analyzed. Pooled data were tested with weighted ANOVA and ANCOVA models for differences in perfusion results between normal pancreas, pancreatitis, PDAC (pancreatic ductal adenocarcinoma), and non-PDAC (e.g., neuroendocrine tumors, insulinomas) and based on study parameters.

RESULTS: Reported acquisition parameters were heterogeneous, except for contrast agent amount and injection rate. Tube potential and slice thickness decreased, whereas tube current time product and scan coverage increased over time. Blood flow and blood volume showed significant differences between pathologies (both p < 0.001), unlike permeability (p = 0.11). Study parameters showed a significant effect on reported quantitative measurements (p < 0.05).

CONCLUSIONS: Significant differences in perfusion measurements between pathologies could be shown for pooled data despite observed heterogeneity in study parameters. Statistical analysis indicates most influential parameters for future optimization and standardization of acquisition protocols.

CRITICAL RELEVANCE STATEMENT: Quantitative CT perfusion enables differentiation of pancreatic pathologies despite the heterogeneity of study parameters in current clinical practice.

PMID:37477754 | PMC:PMC10361925 | DOI:10.1186/s13244-023-01471-0

The comparison of three different molecular imaging methods in localization and grading of insulinoma

Fetched: July 18th, 2023, 5:02am GMT by Lina Chang

Front Endocrinol (Lausanne). 2023 Jun 30;14:1163176. doi: 10.3389/fendo.2023.1163176. eCollection 2023.

ABSTRACT

AIMS: This cross-sectional study compared the value of molecular imaging (Exendin-4 positron emission tomography/computed tomography [PET/CT], ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F- fluorodeoxyglucose [FDG] PET/CT) in insulinoma localization by stratified tumor size and grading, and explored the correlation of the related the maximum standardized uptake value (SUVmax) with insulinoma grading, Ki-67, maximum tumor diameter, and glucose metabolism.

METHODS: In 28 insulinoma patients, the sensitivity of three types of PET/CT for localizing insulinoma was calculated according to tumor size and grade. We compared the SUVmax for different insulinoma grades and analyzed the correlation of SUVmax with Ki-67, maximum tumor diameter, and glucose metabolism indicators.

RESULTS: The study included 12 grade (G) 1 and 16 G2 cases, with maximum tumor diameters ranging from 9 to 40 mm. Without differentiation by size and grade, the sensitivity of Exendin-4 PET/CT to localize insulinoma was 100%, which significantly exceeded that of ⁶⁸Ga-DOTATATE PET/CT and ¹⁸F-FDG PET/CT (75% and 57%, respectively). In tumors with a maximum diameter ≤ 20 mm and ≤ 15 mm, the sensitivity of Exendin-4 (both 100%) significantly exceeded that of ⁶⁸Ga-DOTATATE PET/CT (74% and 64%, respectively) and ¹⁸F-FDG PET/CT (54% and 50%, respectively). In G1 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of ¹⁸F-FDG PET/CT, but not that of ⁶⁸Ga-DOTATATE PET/CT, while in G2 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of both other types. However, all three PET/CT types missed a metastatic lymph node in one patient. The ¹⁸F-FDG PET/CT SUVmax was significantly lower than that of the other PET/CT types and that of ⁶⁸Ga-DOTATATE PET/CT was significantly lower in G2 than in G1. ⁶⁸Ga-DOTATATE PET/CT SUVmax correlated negatively with Ki-67. A receiver operating characteristic (ROC) curve suggested that ⁶⁸Ga-DOTATATE PET/CT SUVmax > 19.9 could predict G1 tumors.

CONCLUSION: Exendin-4 PET/CT was superior to ⁶⁸Ga-DOTATATE PET/CT and ¹⁸F-FDG PET/CT for insulinoma localization, particularly small and G2 tumors, but its diagnostic value in small metastatic lymph nodes requires further exploration. ⁶⁸Ga-DOTATATE PET/CT SUVmax could be used as an adjunct to pathology, and a value > 19.9 could predict G1 tumors. No PET/CT SUVmax could predict tumor maximum diameter and glucose metabolism.

PMID:37455905 | PMC:PMC10348808 | DOI:10.3389/fendo.2023.1163176

Right-Side Acquired Diaphragmatic Hernia in an Adult 15 Years After Living Donor Liver Transplant

Fetched: July 18th, 2023, 5:02am GMT by Yuki Ohya

Exp Clin Transplant. 2023 Jun;21(6):537-539. doi: 10.6002/ect.2023.0029.

ABSTRACT

Cases of adult liver transplant recipients with a postoperative right-side acquired diaphragmatic hernia are extremely rare. In this report, we describe an adult case of right-side acquired diaphragmatic hernia 15 years after living donor liver transplant. A 27-year-old woman was diagnosed with pancreatic insulinoma with multiple metastases in the liver. To treat the liver failure, she underwent left lobe living donor liver transplant and distal pancreatectomy with splenectomy 3 years after the transcatheter arterial chemoembolization. As a result of the liver abscesses that reached the diaphragm, the delicate diaphragm was injured, which required repair during the transplant surgery. At the age of 46 years, she developed a cough and intermittent abdominal pain. One month later, she went to another hospital's emergency room with complaints of epigastric pain. The computed tomography scan revealed colon and small intestine prolapse into the right thoracic cavity. She was referred to our hospital and underwent surgery the next day. Two adjacent right diaphragm defects were successfully sutured with nonabsorbable sutures. The patient was discharged on postoperative day 11.

PMID:37455473 | DOI:10.6002/ect.2023.0029

Permalink for 'Novel Use of Dasiglucagon, a Soluble Glucagon Analog, for the Treatment of Hyperinsulinemic Hypoglycemia Secondary to Suspected Insulinoma: A Case Report'

Novel Use of Dasiglucagon, a Soluble Glucagon Analog, for the Treatment of Hyperinsulinemic Hypoglycemia Secondary to Suspected Insulinoma: A Case Report

Fetched: July 17th, 2023, 5:02am GMT by Dana Reynolds

Horm Res Paediatr. 2023 Jul 14:1-8. doi: 10.1159/000531251. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in children and adults. In adolescents and adults, hyperinsulinemic hypoglycemia is most frequently caused by an insulin-producing tumor.

CASE PRESENTATION: A 17-year-old, previously healthy male presented with recurrent and severe episodes of hypoglycemia. Diagnostic evaluation was consistent with hyperinsulinemic hypoglycemia, and an insulinoma was suspected. Multiple imaging studies and surgical exploration failed to identify a lesion. Over the course of months, the patient was found to be refractory to conventional medical interventions.

CONCLUSION: Upon approval from the US Food and Drug Administration and the Institutional Review Board, the patient was treated with dasiglucagon, a novel soluble glucagon analog, under a single-patient Investigational New Drug. The patient has tolerated the medication and has been able to achieve appropriate glycemic control.

PMID:37454652 | DOI:10.1159/000531251

Permalink for 'Synergistic effect of schizandrin A and DNase I knockdown on high glucose induced beta cell apoptosis by decreasing intracellular calcium concentration'

Synergistic effect of schizandrin A and DNase I knockdown on high glucose induced beta cell apoptosis by decreasing intracellular calcium concentration

Fetched: July 17th, 2023, 5:02am GMT by Zhu Bin

J Tradit Chin Med. 2023 Aug;43(4):661-666. doi: 10.19852/j.cnki.jtcm.2023.04.003.

ABSTRACT

OBJECTIVE: To explore the synergistic effect of deoxyribonuclease I (DNase I) knockdown combined with Schizandrin A (Sch A) in protecting islet beta-cells (β-cells) from apoptosis under high-glucose (HG) conditions.

METHODS: The concentration of Sch A was detected by Cell Counting Kit-8 (CCK-8). High glucose-cultured rat insulinoma beta cell line (RIN-M5F) cells were treated with Sch A and transfected with DNase I small interfering RNA (siRNA). Cell apoptosis rate and apoptosis-related protein level were examined by flow cytometry and Western blot method respectively. In addition, Na-K-adenosine triphosphatease (Na-K-ATPase) and Ca-Mg-ATPase activity, cell membrane potential, and intracellular Ca concentration was also examined respectively.

RESULTS: Our study revealed that HG stimulation can cause a significant increase in DNase I level and cell apoptosis rate. However, Sch A combined with DNase I knockdown can significantly decrease the cell apoptosis rate and apoptosis-related protein levels such as BAX ( 0.05) and Caspase-3 ( 0.01). In addition, we also found that the combination of Sch A and DNase I knockdown can dramatically increase cell membrane potential level, Na-K-ATPase, and Ca-Mg-ATPase activity. Meanwhile, intracellular Ca concentration was also found to be significantly decreased by the synergistic effect of Sch A and DNase I knockdown.

CONCLUSION: Overall, our study reveals a synergistic effect of Sch A and DNase I knockdown in protecting β-cells from HG-induced apoptosis.

PMID:37454250 | PMC:PMC10320450 | DOI:10.19852/j.cnki.jtcm.2023.04.003

Permalink for 'Relevance of Endoscopic Ultrasound in Endocrinology Today: Multiple Endocrine Neoplasia Type 1, Insulinoma, Primary Aldosteronism-An Expert's Perspective Based on Three Decades of Scientific and Clinical Experience'

Relevance of Endoscopic Ultrasound in Endocrinology Today: Multiple Endocrine Neoplasia Type 1, Insulinoma, Primary Aldosteronism-An Expert's Perspective Based on Three Decades of Scientific and Clinical Experience

Fetched: July 15th, 2023, 5:02am GMT by Peter Herbert Kann

Cancers (Basel). 2023 Jul 4;15(13):3494. doi: 10.3390/cancers15133494.

ABSTRACT

In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and to identify aldosterone-producing adenomas. EUS in endocrinology requires special skills and individual experience in order to provide reliable diagnostic information.

PMID:37444604 | PMC:PMC10340175 | DOI:10.3390/cancers15133494

Hypoglycaemia in non-diabetic pregnancy

Fetched: July 14th, 2023, 5:02am GMT by Adam Morton

Obstet Med. 2023 Jun;16(2):123-125. doi: 10.1177/1753495X211032787. Epub 2021 Aug 14.

ABSTRACT

Hypoglycaemia in non-diabetic pregnancy is rare, the majority of reported cases being due to insulinoma, acute fatty liver of pregnancy, malaria and inborn errors of metabolism. A case of hypoglycaemia in a woman with previous laparoscopic sleeve gastrectomy, and hypothalamic-pituitary-adrenal axis insufficiency in the setting of opioid dependence is presented. The timing of low interstitial glucose levels was atypical for late dumping syndrome following bariatric surgery, and a change in the woman's glucocorticoid replacement resulted in resolution of hypoglycaemic symptoms. The incidence of opioid dependence in pregnancy is increasing rapidly. Health professionals should be aware of the possibility of opioids causing hypothalamic-pituitary-adrenal axis insufficiency, and the additional mechanisms by which opioids may cause hypoglycaemia.

PMID:37441658 | PMC:PMC10334043 | DOI:10.1177/1753495X211032787

Ectopic insulinoma: a systematic review

Fetched: July 12th, 2023, 5:02am GMT by Fernando Guerrero-Pérez

Rev Endocr Metab Disord. 2023 Jul 12. doi: 10.1007/s11154-023-09824-2. Online ahead of print.

ABSTRACT

Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [⁶⁸Ga]Ga-DOTA-exedin-4 PET/CT (100%), ⁶⁸Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [⁶⁸Ga]Ga-DOTA-exedin-4 PET/CT and ⁶⁸Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.

PMID:37434098 | DOI:10.1007/s11154-023-09824-2

Differences in clinical characteristics, treatment, and outcomes of sporadic and MEN-1-related insulinomas

Fetched: July 12th, 2023, 5:02am GMT by Marta Opalińska

Endokrynol Pol. 2023 Jul 11. doi: 10.5603/EP.a2023.0049. Online ahead of print.

ABSTRACT

INTRODUCTION: Although in most cases insulinomas are small, benign, sporadic tumours, they can also be associated with hereditary syndromes, most commonly multiple endocrine neoplasia type 1 (MEN-1). Such a diagnosis significantly affects patient management. The objective was to elucidate the clinical differences between sporadic and MEN-1-linked insulinoma.

MATERIAL AND METHODS: Comparison of clinical and histopathological characteristics, types of surgery, and outcomes of patients with sporadic and MEN-1-related insulinoma diagnosed between 2015 and 2022.

RESULTS: There were 17 cases of insulinomas that underwent MEN-1 genetic testing (10 women and 7 men). In 7 cases, the mutation in the menin gene was confirmed. The median age at the time of diagnosis of sporadic insulinoma related to MEN-1 was 69 years (range 29-87) and 31.5 years (16-47), respectively. Primary hyperparathyroidism (PHP) was found in 6 of 7 patients with MEN-1-related insulinoma, while in none of the patients without MEN-1 mutations. Multifocal pancreatic NETs were found in 3 patients with MEN-1 syndrome, while in all sporadic cases there was a single pancreatic tumour. Two patients with insulinoma related to MEN-1 had a positive familial history of MEN-1-related diseases, while none with sporadic form. Dissemination at diagnosis was found in 4 cases, including 3 patients with insulinoma related to MEN-1-related insulinoma. Patients with sporadic and MEN-1-related insulinoma did not differ in tumour size, Ki-67 proliferation index, and outcome.

CONCLUSIONS: Of all the features evaluated, only the multifocal nature of pancreatic neuroendocrine tumour (PanNET) lesions and a positive family history differentiated between patients with sporadic and MEN-1-related insulinomas. An age of insulinoma diagnosis of less than 30 years may be a strong indicator of an increased risk of MEN-1 syndrome.

PMID:37431872 | DOI:10.5603/EP.a2023.0049

Robotic versus laparoscopic surgery for sporadic benign insulinoma: Short- and long-term outcomes

Fetched: July 10th, 2023, 5:02am GMT by Zhu-Zeng Yin

Hepatobiliary Pancreat Dis Int. 2023 Jul 3:S1499-3872(23)00110-8. doi: 10.1016/j.hbpd.2023.06.012. Online ahead of print.

ABSTRACT

BACKGROUND: Minimally invasive surgery is the optimal treatment for insulinoma. The present study aimed to compare short- and long-term outcomes of laparoscopic and robotic surgery for sporadic benign insulinoma.

METHODS: A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was conducted. The demographic, perioperative and postoperative follow-up results were compared between the laparoscopic and robotic groups.

RESULTS: A total of 85 patients were enrolled, including 36 with laparoscopic approach and 49 with robotic approach. Enucleation was the preferred surgical procedure. Fifty-nine patients (69.4%) underwent enucleation; among them, 26 and 33 patients underwent laparoscopic and robotic surgery, respectively. Robotic enucleation had a lower conversion rate to laparotomy (0 vs. 19.2%, P = 0.013), shorter operative time (102.0 vs. 145.5 min, P = 0.008) and shorter postoperative hospital stay (6.0 vs. 8.5 d, P = 0.002) than laparoscopic enucleation. There were no differences between the groups in terms of intraoperative blood loss, the rates of postoperative pancreatic fistula and complications. After a median follow-up of 65 months, two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a recurrence.

CONCLUSIONS: Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time, which might lead to a reduction in postoperative hospital stay.

PMID:37423832 | DOI:10.1016/j.hbpd.2023.06.012

Permalink for 'Prevalence of Positivity for Diabetes-Associated Autoantibodies in Individuals with Type 2 Diabetes and Their Further Characterisation: Cross-sectional Study from Slovakia'

Prevalence of Positivity for Diabetes-Associated Autoantibodies in Individuals with Type 2 Diabetes and Their Further Characterisation: Cross-sectional Study from Slovakia

Fetched: July 9th, 2023, 5:02am GMT by Mariana Rončáková

Diabetes Ther. 2023 Sep;14(9):1537-1548. doi: 10.1007/s13300-023-01440-2. Epub 2023 Jul 8.

ABSTRACT

BACKGROUND: Individuals initially diagnosed with type 2 diabetes (T2D) might exhibit positivity for diabetes-associated autoantibodies (DAA +). We investigated the prevalence of DAA positivity in a group of individuals with T2D who were referred to a tertiary diabetes centre within a pre-specified period of time. We aimed to identify characteristics linked with DAA positivity by comparing DAA + individuals with their DAA-negative counterparts.

METHODS: This was a cross-sectional study into which all T2D patients referred to the National Institute of Endocrinology and Diabetology, Ľubochňa, Slovakia, between 1 January and 30 June 2016 were included. Data on > 70 participants' characteristics, including antibodies against glutamic acid decarboxylase (anti-GAD65), insulinoma-associated antigen IA-2 (IA-2A) and insulin (IAA), were collected.

RESULTS: Six hundred and ninety-two individuals (387, 55.6% female) with a median (range) age of 62 (24-83) years, HbA1c of 8.9 (5.0-15.7)% [74 (31-148 mmol/mol)] and diabetes duration of 13.0 (0-42) years were analysed. One hundred and forty-five (145/692, 21.0%) tested positive for at least one DAA; 136/692 (19.7%) were positive for anti-GAD65, 21/692 (3.0%) were positive for IA-2A and 9/692 (1.3%) were positive for IAA. Only 84.9% of the DAA + individuals aged > 30 years at the time of diabetes diagnosis met the current diagnostic criteria for latent autoimmune diabetes of adults (LADA). DAA + differed from DAA - individuals in multiple characteristics, including the incidence of hypoglycaemia.

CONCLUSION: Several pathological processes linked with distinct types of diabetes can develop in parallel, including insulin resistance and autoimmune insulitis. In this single-centre cross-sectional study from Slovakia, we report a higher than previously published prevalence of DAA positivity in a group of individuals with a formal diagnosis of T2D.

PMID:37421585 | PMC:PMC10363090 | DOI:10.1007/s13300-023-01440-2

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