Rare Cancer News & Clinical Trials

Pancreas (189 unread)

177Lu-DOTATOC for the Treatment of Patients With Somatostatin Receptor Positive NETs

Posted: June 7th, 2021, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Carcinoid Tumor; Pulmonary Carcinoid Tumor; Gastroenteropancreatic Neuroendocrine Tumor; Vipoma; Insulinoma; Gastrinoma
Intervention: Drug: 177Lu-DOTATOC
Sponsor: British Columbia Cancer Agency
Not yet recruiting

Exenatide-test for Diagnosing Endogenous Hyperinsulinemic Hypoglycemia

Posted: May 31st, 2021, 2:00pm GMT

Condition: Insulinoma Patients
Interventions: Drug: Exenatide; Drug: 0.9% saline solution
Sponsors: University Hospital, Basel, Switzerland; Gottfried und Julia Bangerter-Rhyner-Stiftung
Recruiting

Diagnosing and Treating Low Blood Sugar Levels

Posted: November 4th, 1999, 3:00pm GMT

Conditions: Hypoglycemia; Insulinoma
Intervention:
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruiting

Quercetin improves oxidative stress-induced pancreatic beta cell alterations via mTOR-signaling

Fetched: June 16th, 2021, 5:02am GMT by R Dhanya

Mol Cell Biochem. 2021 Jun 15. doi: 10.1007/s11010-021-04193-3. Online ahead of print.

ABSTRACT

Citrus flavonoids particularly quercetin which is abundant in grapefruit, onion, green tea, berries etc. are known to have a protective effect on oxidative stress. Pancreatic β cells which synthesize and secrete insulin are prone to oxidative stress induced damage because of low cellular antioxidant enzymes. To delineate the effects of quercetin on pancreatic β cells we evaluated the protective effect of quercetin on TC6 insulinoma cells subjected to oxidative stress induced by tert-butyl-hydrogen-peroxide (TBHP). Quercetin was found to reduce TBHP induced apoptosis and trigger insulin secretion in response to glucose, in a dose-dependent manner. Quercetin treatment increased mitochondrial biogenesis, caused hypertrophy in pancreatic β cells and activated mTOR signaling with a transient change in mitochondrial membrane potential and AMP/ATP. Activation of mTOR signaling resulted in enhanced insulin secretion in TC6 cells.

PMID:34129156 | DOI:10.1007/s11010-021-04193-3

An in vitro Perfused Macroencapsulation Device to Study Hemocompatibility and Survival of Islet-Like Cell Clusters

Fetched: June 15th, 2021, 5:01am GMT by Stephanie A Fernandez

Front Bioeng Biotechnol. 2021 May 28;9:674125. doi: 10.3389/fbioe.2021.674125. eCollection 2021.

ABSTRACT

Transplantation of hydrogel-encapsulated pancreatic islets is a promising long-term treatment for type 1 diabetes that restores blood glucose regulation while providing graft immunoprotection. Most human-scale islet encapsulation devices that rely solely on diffusion fail to provide sufficient surface area to meet islet oxygen demands. Perfused macroencapsulation devices use blood flow to mitigate oxygen limitations but increase the complexity of blood-device interactions. Here we describe a human-scale in vitro perfusion system to study hemocompatibility and performance of islet-like cell clusters (ILCs) in alginate hydrogel. A cylindrical perfusion device was designed for multi-day culture without leakage, contamination, or flow occlusion. Rat blood perfusion was assessed for prothrombin time and international normalized ratio and demonstrated no significant change in clotting time. Ex vivo perfusion performed with rats showed patency of the device for over 100 min using Doppler ultrasound imaging. PET-CT imaging of the device successfully visualized metabolically active mouse insulinoma 6 ILCs. ILCs cultured for 7 days under static conditions exhibited abnormal morphology and increased activated caspase-3 staining when compared with the perfused device. These findings reinforce the need for convective transport in macroencapsulation strategies and offer a robust and versatile in vitro system to better inform preclinical design.

PMID:34124024 | PMC:PMC8193939 | DOI:10.3389/fbioe.2021.674125

Permalink for 'Risk factors and prevention of postoperative pancreatic fistula after insulinoma enucleation:a retrospective study from a high-volume center'

Risk factors and prevention of postoperative pancreatic fistula after insulinoma enucleation:a retrospective study from a high-volume center

Fetched: June 13th, 2021, 5:01am GMT by Qiang Xu

Pancreatology. 2021 Jun 5:S1424-3903(21)00475-0. doi: 10.1016/j.pan.2021.06.001. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Enucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation.

METHODS: This retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored.

RESULTS: A cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852-19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028).

CONCLUSIONS: The distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm).

PMID:34116940 | DOI:10.1016/j.pan.2021.06.001

Insulinoma-derived pseudo-islets for diabetes research

Fetched: June 10th, 2021, 5:01am GMT by Nathaniel J Hart

Am J Physiol Cell Physiol. 2021 Jun 9. doi: 10.1152/ajpcell.00466.2020. Online ahead of print.

ABSTRACT

The islets of Langerhans of the pancreas are the primary endocrine organ responsible for regulating whole body glucose homeostasis. The use of isolated primary islets for research development and training requires organ resection, careful digestion and isolation of the islets from non-endocrine tissue. This process is time consuming, expensive and requires substantial expertise. For these reasons, we sought to develop a more rapidly obtainable and consistent model system with characteristic islet morphology and function that could be employed to train personnel and better inform experiments prior to using isolated rodent and human islets. Immortalized β cell lines reflect several aspects of primary β cells, but cell propagation in monolayer cell culture limits their usefulness in several areas of research which depend on islet morphology and/or functional assessment. In this manuscript we describe the propagation and characterization of insulinoma pseudo-islets (IPIs) from a rat insulinoma cell line INS832/3. IPIs were generated with an average diameter of 200 μm, consistent with general islet morphology. The rates of oxygen consumption and mitochondrial oxidation-reduction changes in response to glucose and metabolic modulators were similar to isolated rat islets. In addition, the dynamic insulin secretory patterns of IPIs were similar to primary rat islets. Thus, INS832/3-derived IPIs provide a valuable and convenient model for accelerating islet and diabetes research.

PMID:34106785 | DOI:10.1152/ajpcell.00466.2020

Radiofrequency Ablation as a Primary Therapy for Benign Functioning Insulinoma

Fetched: June 8th, 2021, 5:01am GMT by Ebtihal Y Alyusuf

AACE Clin Case Rep. 2020 Dec 28;7(2):153-157. doi: 10.1016/j.aace.2020.12.003. eCollection 2021 Mar-Apr.

ABSTRACT

OBJECTIVE: Insulinomas are rare, life-threatening pancreatic neuroendocrine tumors. Surgical removal continues to be the treatment of choice, yet it is associated with considerable risk of morbidity. Here, we describe our patient with insulinoma who was successfully treated with radiofrequency ablation.

METHODS: The patient was a 56-year-old man with no history of diabetes mellitus. He presented with recurrent episodes of transient ischemic attacks and stroke over the last 3 years. Some changes in his behavior and memory were noticed by family members. During his hospital stay for the second transient ischemic attack, frequent hypoglycemia was documented, which was asymptomatic. Insulinoma was confirmed biochemically. Radiological findings were also compatible with pancreatic neuroendocrine tumor. Treatment modalities were explained to the patient. However, he strongly refused surgery. Meanwhile, he was admitted because of a stroke and concurrent hypoglycemia again. In view of his refusal of the surgical treatment and due to his presentation with acute stroke and high-risk status for surgery, radiofrequency ablation was finalized.

RESULTS: Radiofrequency ablation of the pancreatic tumor using 40.75 Gy over fractions was performed with a favorable outcome. The patient has achieved biochemical normalization and remained euglycemic during his follow- up. Computed tomography scan of the abdomen during follow-up showed a mild regression of the size of the tumor.

CONCLUSION: This report shows a treatment challenge that required the use of an alternative treatment option other than the standard of care. It highlights the evolving evidence of radiofrequency as a therapeutic modality for patients with insulinoma.

PMID:34095476 | PMC:PMC8053623 | DOI:10.1016/j.aace.2020.12.003

Permalink for 'Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics'

Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics

Fetched: June 5th, 2021, 5:01am GMT by Brian Quattrochi

Am J Dermatopathol. 2021 Jun 2. doi: 10.1097/DAD.0000000000001990. Online ahead of print.

ABSTRACT

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade adnexal malignancy with a predilection for the eyelids of elderly White women, which is associated with invasive mucinous carcinoma with endocrine features in one-third of cases. EMPSGC is characterized by the presence of neuroendocrine differentiation and mucin production. However, EMPSGC displays a variety of architectural patterns including solid, cribriform, papillary, and cystic growth. In addition, EMPSGC may also display nonendocrine cytologic features, such as apocrine change. Because of their variable appearance, EMPSGC can show significant morphologic overlap with certain histologic mimics, namely basal cell carcinoma, hidrocystoma, apocrine hidradenoma, and tubular adenoma. In addition, the often limited sampling of this anatomically delicate area can make the diagnosis of EMPSGC challenging. EMPSGC expresses neuroendocrine markers, including synaptophysin and chromogranin, often in a focal distribution. However, insulinoma-associated protein 1 (INSM1) has been found to be a more sensitive marker for EMPSGC. Recent studies have also demonstrated the expression of the gel-forming mucin 2 (MUC2) in EMPSGC, possibly signifying a lacrimal or conjunctival origin of these neoplasms. In this article, we discuss EMPSGC in the context of its histologic mimics (BCC, hidrocystoma, apocrine hidradenoma, and tubular adenoma) and we investigate the utility of the immunohistochemical expression of INSM1 and MUC2 in the distinction of EMPSGC from them. We demonstrate that INSM1 and MUC2 can reliably distinguish EMPSGC from these histologic mimics.

PMID:34086646 | DOI:10.1097/DAD.0000000000001990

Ultrasound-guided caudal thoracic paravertebral block in a dog with an insulinoma undergoing partial pancreatectomy

Fetched: June 5th, 2021, 5:01am GMT by Nuria Quesada

Vet Anaesth Analg. 2021 May 13:S1467-2987(21)00096-9. doi: 10.1016/j.vaa.2021.04.005. Online ahead of print.

NO ABSTRACT

PMID:34083138 | DOI:10.1016/j.vaa.2021.04.005

Oxytocin signal contributes to the adaptative growth of islets during gestation

Fetched: June 3rd, 2021, 5:01am GMT by Ping Gu

Endocr Connect. 2021 Jun 1:EC-21-0043.R1. doi: 10.1530/EC-21-0043. Online ahead of print.

ABSTRACT

BACKGROUND: Increased insulin production and secretion by pancreatic β-cells are important for ensuring the high insulin demand during gestation. However, the underlying mechanism of β-cell adaptation during gestation or in gestational diabetes mellitus (GDM) remains unclear. Oxytocin is an important physiological hormone in gestation and delivery, and it also contributes to the maintenance of β-cell function. The aim of this study was to investigate the role of oxytocin in β-cell adaptation during pregnancy.

METHODS: The relationship between the blood oxytocin level and pancreatic β-cell function in patients with GDM and healthy pregnant women was investigated. Gestating and non-gestating mice were used to evaluate the in vivo effect of oxytocin signal on β-cells during pregnancy. In vitro experiments were performed on INS-1 insulinoma cells.

RESULTS: The blood oxytocin levels were lower in patients with GDM than in healthy pregnant women and were associated with impaired pancreatic β-cell function. Acute administration of oxytocin increased insulin secretion in both gestating and non-gestating mice. A three-week oxytocin treatment promoted the proliferation of pancreatic β-cells and increased the β-cell mass in gestating but not non-gestating mice. Antagonism of oxytocin receptors by atosiban impaired insulin secretion and induced GDM in gestating but not non-gestating mice. Oxytocin enhanced glucose-stimulated insulin secretion, activated the mitogen-activated protein kinase pathway, and promoted cell proliferation in INS-1 cells.

CONCLUSIONS: These findings provide strong evidence that oxytocin is needed for β-cell adaptation during pregnancy to maintain β-cell function, and lack of oxytocin could be associated with the risk of GDM.

PMID:34077390 | DOI:10.1530/EC-21-0043

Isoprenoid Derivatives of Lysophosphatidylcholines Enhance Insulin and GLP-1 Secretion through Lipid-Binding GPCRs

Fetched: June 3rd, 2021, 5:01am GMT by Anna Drzazga

Int J Mol Sci. 2021 May 27;22(11):5748. doi: 10.3390/ijms22115748.

ABSTRACT

Insulin plays a significant role in carbohydrate homeostasis as the blood glucose lowering hormone. Glucose-induced insulin secretion (GSIS) is augmented by glucagon-like peptide (GLP-1), a gastrointestinal peptide released in response to ingesting nutriments. The secretion of insulin and GLP-1 is mediated by the binding of nutrients to G protein-coupled receptors (GPCRs) expressed by pancreatic β-cells and enteroendocrine cells, respectively. Therefore, insulin secretagogues and incretin mimetics currently serve as antidiabetic treatments. This study demonstrates the potency of synthetic isoprenoid derivatives of lysophosphatidylcholines (LPCs) to stimulate GSIS and GLP-1 release. Murine insulinoma cell line (MIN6) and enteroendocrinal L cells (GLUTag) were incubated with LPCs bearing geranic acid (1-GA-LPC), citronellic acid (1-CA-LPC), 3,7-dimethyl-3-vinyloct-6-enoic acid (GERA-LPC), and (E)-3,7,11-trimethyl- 3-vinyldodeca-6,10-dienoic acid (1-FARA-LPC). Respective free terpene acids were also tested for comparison. Besides their insulin- and GLP-1-secreting capabilities, we also investigated the cytotoxicity of tested compounds, the ability to intracellular calcium ion mobilization, and targeted GPCRs involved in maintaining lipid and carbohydrate homeostasis. We observed the high cytotoxicity of 1-GERA-LPC and 1-FARA-LPC in contrast 1-CA-LPC and 1-GA-LPC. Moreover, 1-CA-LPC and 1-GA-LPC demonstrated the stimulatory effect on GSIS and 1-CA-LPC augmented GLP-1 secretion. Insulin and GLP-1 release appeared to be GPR40-, GPR55-, GPR119- and GPR120-dependent.

PMID:34072220 | PMC:PMC8197866 | DOI:10.3390/ijms22115748

Prognostic transcriptome classes of duodenopancreatic neuroendocrine tumors

Fetched: June 2nd, 2021, 5:01am GMT by Marc Diedisheim

Endocr Relat Cancer. 2021 Jun 1:ERC-21-0051.R1. doi: 10.1530/ERC-21-0051. Online ahead of print.

ABSTRACT

Duodenopancreatic neuroendocrine tumors (DPNETs) aggressiveness is heterogeneous. Tumor grade and extension are commonly used for prognostic determination. Yet, grade classes are empirically defined, with regular up-dates changing the definition of classes. Genomic screening may provide more objective classes, and reflect tumor biology. The aim of this study was to provide a transcriptome classification of DPNETs. We included 66 DPNETs, covering the entire clinical spectrum of the disease in terms of secretion, grade, and stage. Three distinct molecular groups were identified, associated with distinct outcome (log-rank p<0.01): (i) better-outcome DPNETs with pancreatic beta-cell signature. This group was mainly composed of well-differentiated, grade 1 insulinomas; (ii) poor-outcome DPNETs with pancreatic alpha-cell and hepatic signature. This group included all neuroendocrine carcinomas and grade 3 DPNETs, but also some grade 1 and grade 2 DPNETs; and (iii) intermediate-outcome DPNETs with pancreatic exocrine and progenitor signature. This group included grade 1 and grade 2 DPNETs, with some insulinomas. Fibrinogen gene FGA expression was one of the top most expressed liver gene. FGA expression was associated with disease-free survival (HR=1.13, p=0.005), and could be validated on two independent cohorts. This original pathophysiologic insight provides new prognostic classification perspectives.

PMID:34061769 | DOI:10.1530/ERC-21-0051

Permalink for 'The diagnostic utility of INSM1 and GATA3 in discriminating problematic medullary thyroid carcinoma, thyroid and parathyroid lesions'

The diagnostic utility of INSM1 and GATA3 in discriminating problematic medullary thyroid carcinoma, thyroid and parathyroid lesions

Fetched: June 2nd, 2021, 5:01am GMT by Sarah Adel Hakim

Pol J Pathol. 2021;72(1):11-22. doi: 10.5114/pjp.2021.106440.

ABSTRACT

Discriminating thyroid and parathyroid lesions may sometimes pose a diagnostic difficulty. Medullary thyroid carcinomas (MTCs) display various cytologic and architectural features that resemble other thyroid and even rarely some parathyroid neoplasms. Moreover, some MTCs may have negative serum calcitonin, rendering them difficult to diagnose. Hence, to reach an appropriate diagnosis in problematic cases of these three categories - thyroid lesions, MTC and parathyroid lesions - the use of several immunohistochemical panels has been suggested and applied. However, conventional markers are not always conclusive in problematic cases. Thus, in the current study we aim to evaluate the diagnostic utility of using GATA3 and INSM1 (insulinoma-associated protein 1) as novel nuclear markers to be applied as an adjunct in case of histopathologic suspicion. A retrospective study was carried out on samples of lesions from three groups: group 1: thyroid lesions (27), group 2: medullary thyroid carcinoma (25); 1/25 had negative serum levels of calcitonin, and group 3: parathyroid lesions (36). Biopsies were received at the Pathology Laboratory of Ain Shams University Hospitals. INSM1 showed 98% diagnostic accuracy in diagnosing MTC and differentiating it from other thyroid lesions. The case of MTC with negative serum calcitonin showed positive INSM1 staining. GATA3 showed 96.8% diagnostic accuracy in diagnosing parathyroid lesions and differentiating them from thyroid lesions. Using immunohistochemical staining by GATA3 and INSM1, in the appropriate histopathological setting, significantly aids in the differentiation between thyroid lesions, parathyroid lesions and MTCs. INSM1 could serve as a potential diagnostic marker in the rare cases of non-secretory MTC and in metastatic work up.

PMID:34060284 | DOI:10.5114/pjp.2021.106440

Permalink for 'The Shape of the Oral Glucose Tolerance Test-Glucose Response Curve in Islet Cell Antibody-Positive vs. -Negative Obese Youth Clinically Diagnosed with Type 2 Diabetes'

The Shape of the Oral Glucose Tolerance Test-Glucose Response Curve in Islet Cell Antibody-Positive vs. -Negative Obese Youth Clinically Diagnosed with Type 2 Diabetes

Fetched: June 2nd, 2021, 5:01am GMT by Joon Young Kim

J Obes Metab Syndr. 2021 Jun 1. doi: 10.7570/jomes20088. Online ahead of print.

ABSTRACT

BACKGROUND: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if the OGTT-GRC pattern is worse in obese antibody (glutamic acid decarboxylase 65-kDa [GAD65] and insulinoma-associated protein-2 [IA2])-positive (Ab⁺) vs. -negative (Ab^-) youth clinically diagnosed with type 2 diabetes (CDX-T2D).

METHODS: Forty-seven obese youth, 15 Ab⁺ and 32 Ab^-, were divided into three OGTT-GRC groups: incessant increase, monophasic, and biphasic. The prevalence of OGTT-GRC, clamp-measured insulin sensitivity, and β-cell function was compared.

RESULTS: Incessant increase OGTT-GRC is the most frequent curve type and is three-fold higher in Ab⁺ vs. Ab^- youth CDX-T2D. In Ab⁺ youth, there was up to 40% lower second-phase insulin secretion in the incessant increase group vs. the other two groups combined (monophasic and biphasic). In Ab^-, while first- and second-phase insulin secretion was significantly lower in the incessant increase vs. the other two groups combined, overall β-cell function was less impaired than in Ab⁺ youth. In neither Ab^- or Ab⁺ youth was OGTT-GRC related to hepatic or peripheral insulin sensitivity.

CONCLUSION: Severe insulin deficiency, a characteristic of type 1 diabetes, seems to be related to higher prevalence of incessant increase in Ab⁺ vs. Ab^- obese youth.

PMID:34059560 | DOI:10.7570/jomes20088

Permalink for 'Hypoglycemia Associated With Drug-Drug Interactions in Patients With Type 2 Diabetes Mellitus Using Dipeptidylpeptidase-4 Inhibitors'

Hypoglycemia Associated With Drug-Drug Interactions in Patients With Type 2 Diabetes Mellitus Using Dipeptidylpeptidase-4 Inhibitors

Fetched: May 28th, 2021, 5:01am GMT by Chin-Ying Ray

Front Pharmacol. 2021 Apr 15;12:570835. doi: 10.3389/fphar.2021.570835. eCollection 2021.

ABSTRACT

Background: Dipeptidylpeptidase-4 inhibitors (DPP-4i's) are considered to be safe for patients with type 2 diabetes mellitus (T2DM). However, little is known about drug-drug interactions between DPP-4i's and concurrent medications. Methods: Data on patients using DPP-4i's for T2DM during 2011-2017 were retrieved from Chang Gung Research database provided by Chang Gung Memorial Hospital. Patients were excluded if they were aged <30 years or >90 years; had incomplete demographic data; had insulinoma; or had records of concomitant insulin use. A generalized estimating equation-based Poisson model was employed for statistical analysis. The primary outcome was hypoglycemia events. Results: We retrieved data on a total of 97,227 patients using DPP-4i's. After patients were excluded according to the mentioned criteria, the remaining 77,047 DPP-4i users were studied (mean age 64 ± 12 years, men 54.4%). The most common medications coprescribed with DPP4is over all person-quarters were acetaminophen, simvastatin, fluvastatin, and colchicine (all >20,000 person-quarters). The combinations of a DPP-4i with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were associated with an increased risk of hypoglycemia. Compared with the ratios observed for person-quarters of DPP-4i use alone (reference category), the adjusted prevalence ratios per 100 person-years of hypoglycemia for person-quarters of DPP-4i use in combination with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were 2.44 (95% confidence interval [CI], 1.78-3.36), 2.97 (95% CI, 2.26-3.90), 1.87 (95% CI, 1.44-2.42), 2.83 (95% CI, 2.44-3.29), 2.27 (95% CI, 1.27-4.04), and 3.03 (95% CI, 1.96-4.68), respectively. Conclusion: Among patients taking DPP-4i's for T2DM, concurrent use of such inhibitors with bumetanide, captopril, acetaminophen, and pantoprazole was associated with an increased risk of hypoglycemia compared with the use of DPP-4i's alone. Physicians prescribing DPP-4i's should consider the potential risks associated with their concomitant use with other drugs.

PMID:34040513 | PMC:PMC8142266 | DOI:10.3389/fphar.2021.570835

MiR-205 is upregulated in islets of diabetes-susceptible mice and targets the diabetes gene Tcf7l2

Fetched: May 25th, 2021, 5:01am GMT by Meriem Ouni

Acta Physiol (Oxf). 2021 May 24:e13693. doi: 10.1111/apha.13693. Online ahead of print.

ABSTRACT

AIM: MicroRNAs play an important role in the maintenance of cellular functions by fine-tuning gene expression levels. The aim of the current study was to identify genetically caused changes in microRNA expression which associate with islet dysfunction in diabetic mice.

METHODS: To identify novel microRNAs involved in islet dysfunction, transcriptome and miRNome analyses were performed in islets of obese, diabetes-susceptible NZO and diabetes-resistant B6-ob/ob mice and results combined with quantitative trait loci (QTL) and functional in vitro analysis.

RESULTS: In islets of NZO and B6-ob/ob mice 94 differentially expressed microRNAs were detected, of which 11 are located in diabetes QTL. Focusing on conserved microRNAs exhibiting the strongest expression difference and which have not been linked to islet function, miR-205-5p was selected for further analysis. According to transcriptome data and target prediction analyses, miR-205-5p affects genes involved in Wnt and calcium signalling as well as insulin secretion. Overexpression of miR-205-5p in the insulinoma cell line INS-1 increased insulin expression and basal insulin secretion and supressed the expression of the diabetes gene TCF7L2. The interaction between miR-205-5p and TCF7L2 was confirmed by luciferase reporter assay.

CONCLUSION: MiR-205-5p was identified as relevant microRNA involved in islet dysfunction by interacting with TCF7L2.

PMID:34028994 | DOI:10.1111/apha.13693

A case of insulinoma with hypoglycemia that was better managed with lanreotide than octreotide

Fetched: May 25th, 2021, 5:01am GMT by Keiko Yamaoka

Clin Case Rep. 2021 May 19;9(5):e04118. doi: 10.1002/ccr3.4118. eCollection 2021 May.

ABSTRACT

Long-acting somatostatin analogs, including lanreotide slow release (LAN-SR) and octreotide long-acting release (OCT-LAR), can improve hypoglycemia in insulinoma. LAN-SR may be more beneficial in some patients with insulinoma than OCT-LAR.

PMID:34026158 | PMC:PMC8133073 | DOI:10.1002/ccr3.4118

Permalink for 'Insulinoma-associated protein 1(INSM1) is a superior marker for the diagnosis of gastroenteropancreatic neuroendoerine neoplasms: a meta-analysis'

Insulinoma-associated protein 1(INSM1) is a superior marker for the diagnosis of gastroenteropancreatic neuroendoerine neoplasms: a meta-analysis

Fetched: May 23rd, 2021, 5:01am GMT by Qinghui Zhang

Endocrine. 2021 May 22. doi: 10.1007/s12020-021-02754-6. Online ahead of print.

ABSTRACT

PURPOSE: An increasing number of studies have shown that insulinoma-associated protein 1 (INSM1) is a robust marker for the diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). The overall diagnostic accuracy of INSM1 for GEP-NEN remains unclear. The purpose of this study is to estimate the diagnostic value of INSM1 for GEP-NEN through a meta-analysis.

METHODS: We searched relevant studies addressing the accuracy of INSM1 in the diagnosis of GEP-NEN from PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) as well as from reference lists since the establishment of the database to January 12, 2021. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves were used to comprehensively evaluate the diagnostic value of INSM1 for GEP-NEN. Statistical analysis was performed by Stata 15.0 and RevMan 5.4.

RESULTS: Nine studies with a total of 393 patients were included in the meta-analysis. The meta-analysis results showed that the pooled sensitivity and specificity of INSM1 for the diagnosis of GEP-NEN were 0.99 (95% CI: 0.87-1.00) and 0.96 (95% CI: 0.93-0.98), respectively. The PLR and NLR were 23.3 (95% CI: 13.3-40.8) and 0.01 (95% CI: 0.00-0.14), respectively. The DOR was 380.31 (95% CI: 164.14-881.21), and the area under the curve (AUC) of SROC curve was 0.98 (95% CI: 0.96-0.99).

CONCLUSIONS: The results show that INSM1 is an effective marker for the diagnosis of GEP-NEN with high sensitivity and specificity. INSM1 is recommended for clinical application to improve the diagnostic accuracy of GEP-NEN. However, more high-quality studies are needed to confirm these findings.

PMID:34021851 | DOI:10.1007/s12020-021-02754-6

Case report of a pancreatic insulinoma misdiagnosed as epilepsy

Fetched: May 21st, 2021, 5:01am GMT by Barbara Anna Williams

BMJ Case Rep. 2021 May 19;14(5):e238238. doi: 10.1136/bcr-2020-238238.

ABSTRACT

A 55-year-old patient had spent 12 years with unexplained seizures, initially diagnosed as epilepsy and then as a psychiatric disorder. When she was admitted with hypoglycaemia, a fasting test was performed showing blood sugar levels as low as 1 mmol/L with symptoms of neuroglycopenia. Insulinoma was suspected and an MRI showed a large tumour in the tail region of the pancreas. A Dodecanetetraacetic acid-Tyr3-octreotate (DOTATATE) positron emission tomography CT indicated no malignancy and showed no signs of metastasis. The patient underwent surgery, leaving her asymptomatic.

PMID:34011656 | PMC:PMC8137184 | DOI:10.1136/bcr-2020-238238

Insulinoma misdiagnosed as epilepsy in 44 Chinese patients

Fetched: May 20th, 2021, 5:01am GMT by Yu-Qing Qu

Neuro Endocrinol Lett. 2021 Mar 19;42(1):43-47. Online ahead of print.

ABSTRACT

OBJECTIVE: Insulinoma is a rare pancreatic neuroendocrine tumor that can spontaneously produce excess endogenous insulin, resulting in recurrent and serious hypoglycemia. Patients with insulinoma always have intermittent neuroglycopenia, which has been frequently reported as being misdiagnosed as epilepsy. In this report, we analyzed the clinical data of patients with confirmed insulinoma who had ever been misdiagnosed to have epilepsy.

METHODS: The retrospective review was performed on 266 patients with confirmed insulinoma at the First Medical Center of Chinese PLA General Hospital between January 2000 and July 2020.

RESULTS: 1. The diagnosis of insulinoma was confirmed in 266 patients. Forty-four patients [male/female=1/1.8, aged (41.25±12.30) years old] were misdiagnosed to have epilepsy, with a misdiagnosis rate of 16.5%. 2. Thirty-eight patients presented with consciousness disorder. Eleven patients presented with palpitation, sweating, and anxiety. Five patients presented with convulsion and 6 patients presented with abnormal behavior and delirium. 3. Twenty-two patients underwent EEG examination. EEG showed spike wave or spike-slow complex wave in 5 patients, decreased α wave and increased slow wave in θ and δ band in 7 patients, and was normal in 10 patients. 4. Thirty-five patients were incorrectly prescribed with AEDs and 22 patients were even misdiagnosed to have refractory epilepsy. 5. All these 44 patients underwent successful surgery, and hypoglycemia symptoms were relieved after insulinoma resection.

CONCLUSION: Patients with insulinoma sometimes share common clinical characteristics with epilepsy. To patients with epilepsy or suspected epilepsy, especially with poor response to ADEs, hypoglycemia caused by insulinoma should be emphasized in the differential diagnosis.

PMID:34009764

Proteoglycan profiling of human, rat and mouse insulin-secreting cells

Fetched: May 18th, 2021, 5:01am GMT by Mahnaz Nikpour

Glycobiology. 2021 May 12:cwab035. doi: 10.1093/glycob/cwab035. Online ahead of print.

ABSTRACT

Proteoglycans (PGs) are proteins with glycosaminoglycan (GAG) chains, such as chondroitin sulfate (CS) or heparan sulfate (HS), attached to serine residues. We have earlier shown that prohormones can carry CS, constituting a novel class of PGs. The mapping of GAG modifications of proteins in endocrine cells may thus assist us in delineating possible roles of PGs in endocrine cellular physiology. With this aim, we applied a glycoproteomic approach to identify PGs, their GAG chains and their attachment sites in insulin-secreting cells. Glycopeptides carrying GAG chains were enriched from human pancreatic islets, rat (INS-1 832/13) and mouse (MIN6, NIT-1) insulinoma cell lines by ion exchange chromatography, depolymerized with GAG lyases, and analyzed by nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS). We identified CS modifications of chromogranin-A (CgA), islet amyloid polypeptide, secretogranin-1 and secretogranin-2, immunoglobulin superfamily member 10, and protein AMBP. Additionally, we identified two HS-modified prohormones (CgA and secretogranin-1), which was surprising, as prohormones are not typically regarded as HSPGs. For CgA, the glycosylation site carried either CS or HS, making it a so-called hybrid site. Additional HS sites were found on syndecan-1, syndecan-4, nerurexin-2, protein NDNF, and testican-1. These results demonstrate that several prohormones, and other constituents of the insulin-secreting cells are PGs. Cell-targeted mapping of the GAG glycoproteome forms an important basis for better understanding of endocrine cellular physiology, and the novel CS and HS sites presented here provide important knowledge for future studies.

PMID:33997891 | DOI:10.1093/glycob/cwab035

Permalink for 'Blocking TLR4-NF-κB pathway protects mouse islets from the combinatorial impact of high fat and fetuin-A mediated dysfunction and restores ability for insulin secretion'

Blocking TLR4-NF-κB pathway protects mouse islets from the combinatorial impact of high fat and fetuin-A mediated dysfunction and restores ability for insulin secretion

Fetched: May 16th, 2021, 5:01am GMT by Alpana Mukhuty

Mol Cell Endocrinol. 2021 Jul 15;532:111314. doi: 10.1016/j.mce.2021.111314. Epub 2021 May 12.

ABSTRACT

Lipid mediated pancreatic β-cell dysfunction during Type 2 diabetes is known to be regulated by activation of TLR4 (Toll Like Receptor 4) and NF-κB (Nuclear factor kappa B). Recently we have reported that MIN6 cells (mouse insulinoma cells) secrete fetuin-A on stimulation by palmitate that aggravates β-cell dysfunction, but the mechanism involved in-vivo has not been demonstrated and thus remained unclear. Here we attempted to dissect the role of palmitate and fetuin-A on insulin secretion using high fat diet (HFD) fed mice model. HFD islets showed curtailed insulin secretion after 20 weeks of treatment with activated TLR4-NF-κB pathway. Further treatment of islets with palmitate raised fetuin-A expression by ~2.8 folds and cut down insulin secretion by ~1.4 folds. However, blocking the activity of TLR4, fetuin-A and NF-κB using specific inhibitors or siRNAs not only restored insulin secretion by ~2 folds in standard diet fed mice islets and MIN6 cells but also evoke insulin secretory ability by ~2.3 folds in HFD islets. Altogether this study demonstrated that blocking TLR4, fetuin-A and NF-κB protect pancreatic β-cells from the negative effects of free fatty acid and fetuin-A and restore insulin secretion.

PMID:33989718 | DOI:10.1016/j.mce.2021.111314

Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review

Fetched: May 15th, 2021, 5:01am GMT by Qun Chen

Cell Biosci. 2021 May 13;11(1):86. doi: 10.1186/s13578-021-00602-8.

ABSTRACT

Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.

PMID:33985581 | PMC:PMC8120816 | DOI:10.1186/s13578-021-00602-8

Surgical management of insulinoma over three decades

Fetched: May 13th, 2021, 5:01am GMT by Anne de Carbonnières

HPB (Oxford). 2021 Apr 27:S1365-182X(21)00113-1. doi: 10.1016/j.hpb.2021.04.013. Online ahead of print.

ABSTRACT

BACKGROUND: This paper reports our experience of the perioperative management of patients with sporadic, non-malignant, pancreatic insulinoma.

METHODS: A retrospective monocentric cohort study was performed from January 1989 to July 2019, including all the patients who had been operated on for pancreatic insulinoma. The preoperative work-up, surgical management, and postoperative outcome were analyzed.

RESULTS: Eighty patients underwent surgery for sporadic pancreatic insulinoma, 50 of which were female (62%), with a median age of 50 (36-70) years. Preoperatively, the tumors were localized in 76 patients (95%). Computed tomography (CT) and magnetic resonance imaging allowed exact preoperative tumor localization in 76% of the patients (64-85 and 58-88 patients, respectively), increasing to 96% when endoscopic ultrasonography was performed. Forty-one parenchyma-sparing pancreatectomies (PSP) (including enucleation, caudal pancreatectomy, and uncinate process resection) and 39 pancreatic resections were performed. The mortality rate was 6% (n = 5), with a morbidity rate of 72%, including 24 severe complications (30%) and 35 pancreatic fistulas (44%). No differences were found between formal pancreatectomy and PSP in terms of postoperative outcome procedures. The surgery was curative in all the patients.

CONCLUSION: CT used in combination with endoscopic ultrasonography allows accurate localization of insulinomas in almost all patients. When possible, a parenchyma-sparing pancreatectomy should be proposed as the first-line surgical strategy.

PMID:33975801 | DOI:10.1016/j.hpb.2021.04.013

Correction to: Dimethyl sulfoxide acutely enhances regulated insulin secretion in the MIN6-K8 mouse insulinoma cell line

Fetched: May 11th, 2021, 5:01am GMT by Christopher M Carmean

Histochem Cell Biol. 2021 May 9. doi: 10.1007/s00418-021-01988-9. Online ahead of print.

NO ABSTRACT

PMID:33969429 | DOI:10.1007/s00418-021-01988-9

Permalink for 'Cyclic AMP-dependent activation of ERK via GLP-1 receptor signalling requires the neuroendocrine cell-specific guanine nucleotide exchanger NCS-RapGEF2'

Cyclic AMP-dependent activation of ERK via GLP-1 receptor signalling requires the neuroendocrine cell-specific guanine nucleotide exchanger NCS-RapGEF2

Fetched: May 8th, 2021, 5:01am GMT by Wenqin Xu

J Neuroendocrinol. 2021 May 6:e12974. doi: 10.1111/jne.12974. Online ahead of print.

ABSTRACT

Cyclic AMP activation of the Rap-Braf-MEK-ERK pathway after signalling initiated by the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP), via the Gs -protein coupled receptor (Gs PCR) PAC1, occurs uniquely through the neuritogenic cAMP sensor Rap guanine nucleotide exchange factor 2 (NCS-RapGEF2) in Neuroscreen-1 (NS-1) neuroendocrine cells. We examined the expression of other Family B Gs PCRs in this cell line and assessed cAMP elevation and neuritogenesis after treatment with their cognate peptide ligands. Exposure of NS-1 cells to the VIPR1/2 agonist vasoactive intestinal polypeptide, or the GLP1R agonist exendin-4, did not induce neuritogenesis, or elevation of cAMP, presumably as a result of insufficient receptor protein expression. Vasoactive intestinal polypeptide and exendin-4 did induce neuritogenesis after transduction of human VIPR1, VIPR2 and GLP1R into NS-1 cells. Exendin-4/GLP1R-stimulated neuritogenesis was MEK-ERK-dependent (blocked by U0126), indicating its use of the cAMP→RapGEF2→ERK neuritogenic signalling pathway previously identified for PACAP/PAC1 signalling in NS-1 cells. NCS-RapGEF2 is expressed in the rodent insulinoma cell lines MIN6 and INS-1, as well as in human pancreatic islets. As in NS-1 cells, exendin-4 caused ERK phosphorylation in INS-1 cells. Reduction in RapGEF2 expression after RapGEF2-shRNA treatment reduced exendin-4-induced ERK phosphorylation. Transcriptome analysis of INS-1 cells after 1 hour of exposure to exendin-4 revealed an immediate early-gene response that was composed of both ERK-dependent and ERK-independent signalling targets. We propose that cAMP signalling initiated by glucagon-like peptide 1 (GLP-1) in pancreatic beta cells causes parallel activation of multiple cAMP effectors, including NCS-RapGEF2, Epac and protein kinase A, to separately control various facets of GLP-1 action, including insulin secretion and transcriptional modulation.

PMID:33960038 | DOI:10.1111/jne.12974

Preoperative stenting in insulinoma located nearby pancreatic duct: a case report and literature review

Fetched: May 8th, 2021, 5:01am GMT by Miroslav Pindura

J Surg Case Rep. 2021 Apr 29;2021(4):rjab121. doi: 10.1093/jscr/rjab121. eCollection 2021 Apr.

ABSTRACT

Insulinoma is a rare functional neuroendocrine tumor of pancreas. The only recommended treatment is surgical removal. We present a case of a 46-year-old female patient who underwent the enucleation of insulinoma localized nearby pancreatic main duct after preoperative endoscopic insertion of pancreatic stent. The tumor was safely identified during the surgery and was enucleated without injury of pancreatic duct or postoperative complications.

PMID:33959252 | PMC:PMC8084425 | DOI:10.1093/jscr/rjab121

Isolation and Proteomics of the Insulin Secretory Granule

Fetched: May 6th, 2021, 5:01am GMT by Nicholas Norris

Metabolites. 2021 Apr 30;11(5):288. doi: 10.3390/metabo11050288.

ABSTRACT

Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood. In the pancreas, insulin is stored in vesicles termed insulin secretory granules (ISGs). In Type 2 diabetes (T2D), defects in insulin action results in peripheral insulin resistance and beta-cell compensation, ultimately leading to dysfunctional ISG production and secretion. ISGs are functionally dynamic and many proteins present either on the membrane or in the lumen of the ISG may modulate and affect different stages of ISG trafficking and secretion. Previously, studies have identified few ISG proteins and more recently, proteomics analyses of purified ISGs have uncovered potential novel ISG proteins. This review summarizes the proteins identified in the current ISG proteomes from rat insulinoma INS-1 and INS-1E cell lines. Here, we also discuss techniques of ISG isolation and purification, its challenges and potential future directions.

PMID:33946444 | PMC:PMC8147143 | DOI:10.3390/metabo11050288

Permalink for 'Evaluation of palliative therapy, alone or in combination with toceranib phosphate, in dogs diagnosed with metastatic or recurrent beta-cell neoplasia'

Evaluation of palliative therapy, alone or in combination with toceranib phosphate, in dogs diagnosed with metastatic or recurrent beta-cell neoplasia

Fetched: May 5th, 2021, 5:01am GMT by D Alonso-Miguel

N Z Vet J. 2021 Jul;69(4):234-239. doi: 10.1080/00480169.2021.1905569. Epub 2021 May 4.

ABSTRACT

AIMS: To compare survival in dogs with recurrent or metastatic insulinomas that were treated with palliative therapy, alone or in combination with toceranib phosphate and to assess tolerability of the combined therapy in dogs.

MATERIALS AND METHODS: Dogs diagnosed with insulinoma were retrospectively identified in the records of the Veterinary Teaching Hospital Complutense (Madrid, Spain). Diagnosis of insulinoma was based on clinical signs of hypoglycaemia, concentrations in serum of glucose <3.3 mmol/L and insulin >10 μIU/mL and presence of a pancreatic mass on diagnostic imaging. Dogs were treated surgically or medically, according to clinical stage established by imaging techniques, and monitored with blood and urine analyses monthly and abdominal ultrasonography every 3 months until death. Dogs that presented with metastatic disease at diagnosis or with recurrent hypoglycaemia after surgery were treated, according to the owner's decision, with one of two treatment protocols: palliative therapy alone (control group, n=7: diet, prednisone, famotidine or omeprazole, ±octreotide) or palliative therapy in combination with toceranib (treatment group, n=5; median dose of toceranib 2.52 mg/kg). Overall survival time (OST) and adverse events were compared between the two treatment groups.

RESULTS: The OST was longer in the treatment group (median 399, min 125, max 476 days) compared to the control group (median 67, min 23, max 387 days; p=0.042). Dogs in the treatment group had a higher incidence of grade 1-2 gastrointestinal toxicity (diarrhoea) than dogs in the control group (p=0.010). In all cases, gastrointestinal toxicity was solved by temporarily discontinuing toceranib.

CONCLUSIONS AND CLINICAL RELEVANCE: The use of toceranib combined with palliative treatment in dogs with suspect metastatic or recurrent insulinomas increased survival time and was adequate tolerated.

PMID:33944682 | DOI:10.1080/00480169.2021.1905569

A case of insulinoma diagnosed postpartum with hypoglycemic symptoms that were masked during pregnancy

Fetched: May 4th, 2021, 5:01am GMT by Tomoe Abe

Clin Case Rep. 2021 Feb 16;9(4):1991-1998. doi: 10.1002/ccr3.3924. eCollection 2021 Apr.

ABSTRACT

The diagnosis of insulinoma in perinatal women can be difficult, as hypoglycemic symptoms may be masked by pregnancy-associated insulin resistance. In addition, when multiple insulinomas are observed, it is necessary to consider the possibility not only of MEN1, but also of insulinomatosis.

PMID:33936628 | PMC:PMC8077346 | DOI:10.1002/ccr3.3924

Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody

Fetched: April 29th, 2021, 5:01am GMT by Yun Cai

Endocr Connect. 2021 May 19;10(5):534-542. doi: 10.1530/EC-20-0650.

ABSTRACT

OBJECTIVE: The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been few clinical reports based on a large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) and T1DM patients with AITD.

METHODS: Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by RIA.

RESULTS: The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P < 0.05) but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P < 0.0001).

CONCLUSIONS: An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.

PMID:33909592 | PMC:PMC8183620 | DOI:10.1530/EC-20-0650

Permalink for 'Hormonal tumor mapping for liver metastases of gastroenteropancreatic neuroendocrine neoplasms: a novel therapeutic strategy'

Hormonal tumor mapping for liver metastases of gastroenteropancreatic neuroendocrine neoplasms: a novel therapeutic strategy

Fetched: April 28th, 2021, 5:01am GMT by Aya Maekawa

J Cancer Res Clin Oncol. 2021 Apr 27. doi: 10.1007/s00432-021-03650-2. Online ahead of print.

ABSTRACT

PURPOSE: In patients with metastatic functional gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), it is unknown what degree of tumor reduction is required to eliminate hormonal symptoms. We aimed to reduce hormonal symptoms derived from advanced GEP-NENs by efficient minimal intervention, constructing a hormonal tumor map of liver metastases.

METHODS: Between 2013 and 2019, we treated 12 insulinoma or gastrinoma patients with liver metastases. Liver segments containing hormone-producing tumors were identified by injecting calcium gluconate via the hepatic arteries and monitoring the change in serum hormone concentration in the three hepatic veins. A greater-than-twofold increase in hormone concentration indicated a tumor-feeding vessel.

RESULTS: Cases included eight insulinomas and four gastrinomas. Primary lesions were functional in three patients and nonfunctional in 9. Nine patients showed hormonal step-up indicating the presence of functional lesions; eight showed step-up in tumor-bearing liver segments, while one with synchronous liver metastases showed step-up only in the pancreatic region. Five patients underwent surgery. Serum hormone concentration decreased markedly after removing the culprit lesions in 3; immediate improvement in hormonal symptoms was achieved in all patients. Three patients with previous surgical treatment who showed step-up underwent transcatheter arterial embolization, achieving temporary improvement of hormonal symptoms. Four patients showed unclear localization of the hormone-producing tumors; treatment options were limited, resulting in poor outcomes.

CONCLUSION: Hormonal tumor mapping demonstrated heterogeneity in hormone production among primary and metastatic tumors of GEP-NENs. Minimally invasive treatment based on hormonal mapping may be a viable alternative to conventional cytoreduction.

PMID:33904982 | DOI:10.1007/s00432-021-03650-2

Feasible laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors

Fetched: April 28th, 2021, 5:01am GMT by Hironori Shiozaki

Mol Clin Oncol. 2021 Jun;14(6):111. doi: 10.3892/mco.2021.2273. Epub 2021 Apr 3.

ABSTRACT

Pancreatic neuroendocrine tumor (PNET) cases are increasing; however, the treatment indication and procedure remain unestablished. The present study evaluated the indication, feasibility and safety of laparoscopic distal pancreatectomy (LDP) with our technique for PNET. A total of 13 patients with insulinoma and nonfunctional PNET <2 cm in diameter who underwent LDP and 13 patients with any size of PNET who underwent open distal pancreatectomy (ODP) between October 2009 and June 2019 were retrospectively reviewed and compared. The median age of patients was 45 (33-61) years, and 14 (54%) patients were male. The median follow-up periods were 70 months for the LDP group and 46 months for the ODP group. The tumor diameter of the patients who underwent LDP for PNET was 18±9 mm compared with 37±25 mm for those who underwent ODP. The operation time, estimated blood loss, and complication were 290.2±115 vs. 337±131 min (P=0.338), 122±172 vs. 649±693 ml (P=0.019) and 31 vs. 54% (P=0.234), respectively. Pancreatic fistula developed in 8% of patients who underwent LDP compared with 31% who underwent ODP (P=0.131). Notably, the postoperative hospitalization period was significantly shorter in the LDP group (11±7 vs. 21±13 days; P=0.022). Tumor grade of 2017 World Health Organization classification (G1/G2/G3/NEC/unknown) was 9/2/0/0/2 for the LDP group compared with 5/5/0/3/0 for the ODP group. Furthermore, lymph node metastasis was detected in only 1 patient who underwent ODP, for whom the maximum tumor diameter was 70 mm and was classified as G2. In addition, 2 patients in the ODP group developed postoperative lung and liver metastases. LDP for PNETs of <2 cm in selected patients can be safely performed; however, the extent of lymph node dissection needs to be clarified.

PMID:33903817 | PMC:PMC8060851 | DOI:10.3892/mco.2021.2273

Comment on: Insulinoma in tuberous sclerosis: an entity not to be missed

Fetched: April 27th, 2021, 5:01am GMT by Rabea A Gadelkareem

Saudi Med J. 2021 May;42(5):578. doi: 10.15537/smj.2021.42.5.578.

NO ABSTRACT

PMID:33896790 | DOI:10.15537/smj.2021.42.5.578

Bitter melon fruit extract enhances intracellular ATP production and insulin secretion from rat pancreatic β-cells

Fetched: April 27th, 2021, 5:01am GMT by Takumi Shimada

Br J Nutr. 2021 Mar 25:1-7. doi: 10.1017/S0007114521001082. Online ahead of print.

ABSTRACT

Bitter melon (Momordica charantia L.) has been shown to have various health-promoting activities, including antidiabetic and hypoglycaemic effects. Improvement in insulin sensitivity and increase in glucose utilisation in peripheral tissues have been reported, but the effect on insulin secretion from pancreatic β-cells remains unclear. In this study, we investigated the effect of bitter melon fruit on insulin secretion from β-cells and the underlying mechanism. The green fruit of bitter melon was freeze-dried and extracted with methanol. The bitter melon fruit extract (BMFE) was fractionated using ethyl acetate (fraction A), n-butanol (fraction B) and water (fraction C). Insulin secretory capacity from INS-1 rat insulinoma cell line and rat pancreatic islets, as well as glucose tolerance in rats by oral glucose tolerance test (OGTT), was measured using BMFE and fractions. ATP production in β-cells was also examined. BMFE augmented insulin secretion from INS-1 cells in a dose-dependent manner. The significant augmentation of insulin secretion was independent of the glucose dose. Fraction A (i.e. hydrophobic fraction), but not fractions B and C, augmented insulin secretion significantly at the same level as that by BMFE. This finding was also observed in pancreatic islets. In OGTT, BMFE and fraction A decreased blood glucose levels and increased serum insulin levels after glucose loading. The decrease in blood glucose levels was also observed in streptozotocin-induced diabetic rats. In addition, BMFE and fraction A increased the ATP content in β-cells. We concluded that hydrophobic components of BMFE increase ATP production and augment insulin secretion from β-cells, consequently decreasing blood glucose levels.

PMID:33762029 | DOI:10.1017/S0007114521001082

A case report on a protracted course of a hidden insulinoma

Fetched: April 20th, 2021, 5:01am GMT by Fatimah Zaherah Mohamed Shah

Ann Med Surg (Lond). 2021 Mar 24;64:102240. doi: 10.1016/j.amsu.2021.102240. eCollection 2021 Apr.

ABSTRACT

INTRODUCTION: Insulinoma is a functioning pancreatic neuroendocrine tumor primarily leading due to hypoglycemia due to hypersecretion of insulin. This case illustrates the real challenges faced in the detection of an occult insulinoma, which resulted in a protracted course of the disease.

CASE PRESENTATION: A 33-year-old female presented with recurrent hypoglycemia. Endogenous hyperinsulinemia was confirmed by a prolonged fast, however serial imaging was negative. Incidental finding of an ovarian mass gave rise to the suspicion of an insulin-producing ovarian tumor. Subsequent multimodality pancreatic imaging remained negative, requiring more invasive investigations. The tumor was localized by specialized arteriography using calcium stimulation to support the diagnosis of an insulinoma. However, repeated negative imaging led to further delays in definitive management, with worsening hypoglycemia. The surgery was finally performed three years after the initial presentation with successful removal of the tumor using intra-operative ultrasound.

CLINICAL DISCUSSION: It is important to emphasize that preoperative radiological imaging is useful to localize pancreatic lesions. However, most insulinomas could only be detected intraoperatively. The absence of suggestive radiological evidence should not deter surgeons from proceeding with definitive surgical intervention.

CONCLUSION: The case highlights the importance of a multidisciplinary approach in the management of a complicated case.

PMID:33868680 | PMC:PMC8040123 | DOI:10.1016/j.amsu.2021.102240

Application of INSM1 in Diagnosis and Grading of Laryngeal Neuroendocrine Carcinoma

Fetched: April 14th, 2021, 5:02am GMT by Cuncun Yuan

Laryngoscope. 2021 Apr 13. doi: 10.1002/lary.29554. Online ahead of print.

ABSTRACT

OBJECTIVE: Chromogranin (CHG), synaptophysin (Syn), and CD56 are generally used in a panel to support diagnoses of laryngeal neuroendocrine carcinomas (NECs). However, the absence of expression of these markers does not completely exclude the diagnosis. INSM1 is a novel marker that is considered sufficiently sensitive and specific for NE differentiation. The aim of this study is not only to detect its sensitivity and specificity, but also to evaluate its application in grading for laryngeal NECs.

METHODS: The clinicopathological characteristics of the 25 cases with laryngeal NECs were retrospectively analyzed. The expressions of INSM1, CHG, Syn, and CD56 were detected by immunohistochemistry.

RESULTS: Of the 25 laryngeal NECs, INSM1 had higher sensitivity (92%) than Syn (84%), CHG (76%) and CD56 (76%). The average H scores of INSM1, CD56, Syn, and CHG were 160, 37.5, 300, 300 for well-differentiated neuroendocrine carcinoma (WD-NEC); 190, 149, 209, 215 for moderately differentiated neuroendocrine carcinoma (MD-NEC); 251, 208, 104, 25 for poorly differentiated neuroendocrine carcinoma with small cell (SCNEC); 109, 160, 98, 26 for large cell types (LCNEC), respectively. Of these 98 non-neuroendocrine tumors, INSM1 expression was seen in nine (9%) tumors, all were squamous cell carcinoma. And INSM1 staining was generally focal.

CONCLUSION: INSM1 has high sensitivity and specificity in diagnosis of laryngeal NECs. For grading laryngeal NECs, Syn and CHG showed significant advantages in the diagnosis of WD-NEC and MD-NEC, whereas INSM1 and CD56 showed greater diagnostic value in the diagnosis of SCNEC and LCNEC, especially in SCNEC.

LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

PMID:33847383 | DOI:10.1002/lary.29554

Permalink for 'A Giant Borderline Phyllodes Tumor of Breast With Skin Ulceration Leading to Non-Insular Tumorigenic Hypoglycemia: A Case Report and Literature Review'

A Giant Borderline Phyllodes Tumor of Breast With Skin Ulceration Leading to Non-Insular Tumorigenic Hypoglycemia: A Case Report and Literature Review

Fetched: April 13th, 2021, 5:02am GMT by Jinlu Zhao

Front Endocrinol (Lausanne). 2021 Mar 25;12:651568. doi: 10.3389/fendo.2021.651568. eCollection 2021.

ABSTRACT

Phyllodes tumor (PT) is a special type of breast tumors, including three types: malignant, borderline, and benign. Most of these tumors form unilateral disease and can rapidly increase in size. The occurrence of axillary lymph node metastasis is rare. Tumor-associated hypoglycemia can be divided into non-islet cell tumor and insulinoma. In non-islet cell tumor hypoglycemia (NICTH), a considerable high molecular weight form of insulin like growth factor 2 (IGF-2) is formed, which abnormally binds to insulin receptors in the tissues and causes hypoglycemia. Breast phyllodes tumors with NICTH are rare and first reported in 1983. Surgical resection is the main treatment and hypoglycemia symptoms usually resolve after surgery. Nevertheless, prior to surgery, intravenous glucose infusion is used to maintain blood glucose levels. A female patient presented with a rapidly growing breast mass and was diagnosed with a phyllodes tumor with NICTH at our hospital in August 2020; she was successfully treated through surgical resection. We reviewed the relevant literature to investigate and analyze the relationship between NICTH and phyllodes tumors, as well as optimize its diagnosis and treatment.

PMID:33841338 | PMC:PMC8027481 | DOI:10.3389/fendo.2021.651568

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan

Fetched: April 11th, 2021, 5:01am GMT by Tomader Ali Mohammed Ibrahim

Pediatr Diabetes. 2021 Apr 10. doi: 10.1111/pedi.13209. Online ahead of print.

ABSTRACT

OBJECTIVE: To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents.

RESEARCH DESIGN AND METHODS: Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D.

RESULTS: Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10^-14 ). Five HLA-DRB1 alleles exhibited significant T1D association: three alleles (DRB1*03:01, DRB1*04:02, and DRB1*04:05) were positively associated, while three (DRB1*10:01, DRB1*15:02, and DRB1*15:03) were protective. DRB1*03:01 had the strongest association (odds ratio = 5.04, p = 1.7 × 10^-10 ).

CONCLUSIONS: Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

PMID:33837995 | DOI:10.1111/pedi.13209

Permalink for 'In pancreatic β-cells myosin 1b regulates glucose-stimulated insulin secretion by modulating an early step in insulin granule trafficking from the Golgi'

In pancreatic β-cells myosin 1b regulates glucose-stimulated insulin secretion by modulating an early step in insulin granule trafficking from the Golgi

Fetched: April 8th, 2021, 5:02am GMT by Hiroshi Tokuo

Mol Biol Cell. 2021 Jun 1;32(12):1210-1220. doi: 10.1091/mbc.E21-03-0094. Epub 2021 Apr 7.

ABSTRACT

Pancreatic β-cells secrete insulin, which controls blood glucose levels, and defects in insulin secretion are responsible for diabetes mellitus. The actin cytoskeleton and some myosins support insulin granule trafficking and release, although a role for the class I myosin Myo1b, an actin- and membrane-associated load-sensitive motor, in insulin biology is unknown. We found by immunohistochemistry that Myo1b is expressed in islet cells of the rat pancreas. In cultured rat insulinoma 832/13 cells, Myo1b localized near actin patches, the trans-Golgi network (TGN) marker TGN38, and insulin granules in the perinuclear region. Myo1b depletion by small interfering RNA in 832/13 cells reduced intracellular proinsulin and insulin content and glucose-stimulated insulin secretion (GSIS) and led to the accumulation of (pro)insulin secretory granules (SGs) at the TGN. Using an in situ fluorescent pulse-chase strategy to track nascent proinsulin, Myo1b depletion in insulinoma cells reduced the number of (pro)insulin-containing SGs budding from the TGN. The studies indicate for the first time that in pancreatic β-cells Myo1b controls GSIS at least in part by mediating an early stage in insulin granule trafficking from the TGN.

PMID:33826361 | DOI:10.1091/mbc.E21-03-0094

Permalink for 'Meteorin-Like Ameliorates β Cell Function by Inhibiting β Cell Apoptosis of and Promoting β Cell Proliferation via Activating the WNT/β-Catenin Pathway'

Meteorin-Like Ameliorates β Cell Function by Inhibiting β Cell Apoptosis of and Promoting β Cell Proliferation via Activating the WNT/β-Catenin Pathway

Fetched: April 6th, 2021, 5:01am GMT by Wenchao Hu

Front Pharmacol. 2021 Mar 17;12:627147. doi: 10.3389/fphar.2021.627147. eCollection 2021.

ABSTRACT

Meteorin-like (Metrnl) is a newly discovered myokine. Plasma Metrnl is decreased in subjects with newly diagnosed type 2 diabetes (T2D) and correlated with insulin resistance. This study aims to determine the effects of Metrnl on the apoptosis and proliferation of β cell. Mouse insulinoma MIN6 cells were divided into six groups: normal control, low glucose, high glucose, Vehicle, Metrnl, and Dickkopf 1 (DKK1) groups. MIN6 cells in Metrnl group were transfected with recombinant pCDH-Metrnl vector. WNT/β-catenin pathway was inhibited using DKK1. Then the apoptosis of MIN6 cells was detected using flow cytometry and TUNEL labeling. Immunofluorescence of Ki67 or Edu-594 was used to determine the β cell proliferation. db/db mice were confirmed as T2D group. Lentivirus-Metrnl was injected from the caudal vein of db/db mice once every two weeks for two times. High glucose induced the apoptosis of MIN6 cells and elevated expression of caspase 3. In addition, high glucose resulted in reduced β cell proliferation, cell viability, insulin secretion as well as decreased expression of β-catenin and TCF4. Metrnl ameliorated the above effects of high glucose. And the protecting role of Metrnl was inhibited by DKK1. T2D mice showed higher body weight and blood glucose compared with the controls. The β cell apoptosis was increased while the β cell proliferation and WNT/β-catenin pathway were inhibited in T2D mice. Metrnl treatment partly reversed the above changes in T2D mice. Metrnl ameliorates β cell function by inhibiting β cell apoptosis of and promoting β cell proliferation via activating the WNT/β-catenin pathway.

PMID:33815109 | PMC:PMC8010136 | DOI:10.3389/fphar.2021.627147

Pancreatic Islet Function Tests

Fetched: April 6th, 2021, 5:01am GMT by Sai Katta

2021 Mar 16. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Objective: To describe testing indications and protocols for the evaluation of pancreatic islet function. Methods: A review of the literature and consensus guidelines concerning testing of pancreatic islet function was performed. Results: Indications for screening for diabetes mellitus are reviewed. Diagnostic criteria for diagnosis are fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/l) or random glucose ≥200 mg/dl (11.1 mmol/l) with hyperglycemic symptoms, hemoglobin A1c (HbA1c) ≥6.5%, and oral glucose tolerance testing (OGTT) 2-h glucose ≥200 mg/dl (11.1 mmol/l) after 75 g of glucose. One-step and two-step strategies for diagnosing gestational diabetes using pregnancy-specific criteria as well as use of the 2-h 75-g OGTT for the postpartum testing of women with gestational diabetes (4-12 weeks after delivery) are described. Testing for other forms of diabetes with unique features are reviewed, including the recommendation to use the 2-h 75 g OGTT to screen for cystic fibrosis-related diabetes and post-transplantation diabetes, fasting glucose test for HIV positive individuals, and genetic testing for monogenic diabetes syndromes including neonatal diabetes and maturity-onset diabetes of the young (MODY). Elevated measurements of pancreatic islet autoantibodies (e.g., to the 65-KDa isoform of glutamic acid decarboxylase (GAD65), tyrosine phosphatase related islet antigen 2 (IA-2), insulin (IAA), and zinc transporter (ZnT8)) suggest autoimmune type 1 diabetes (vs type 2 diabetes). IAA is primarily measured in youth. The use of autoantibody testing in diabetes screening programs are recommended only in first degree relatives of an individual with type 1 diabetes or in research protocols. C-peptide measurements >3 years after clinician diagnosis of type 1 diabetes in adults can be helpful in identifying those who have type 1 diabetes (low or undetectable c-peptide) from those who may have type 2 or monogenic diabetes. Use of OGTTs to examine insulin secretory reserve and intravenous glucose tolerance testing are also reviewed. These tests are primarily used in research studies. Evaluation of glycemic control is discussed, with special attention to hemoglobin A1c (HbA1c) and its correlation with mean blood glucose levels as well as assays of other glycated serum proteins. Finally, protocols used to evaluate hypoglycemia (glucose < 55 mg/dl (3.1 mmol/l)) are described, such as the supervised prolonged fast, during which measurements of glucose, insulin, c-peptide, oral insulin secretagogues, proinsulin, and beta-hydroxybutyrate are obtained. Insulinoma is suggested by elevated insulin, proinsulin and c-peptide levels, beta-hydroxybutyrate < 2.7 mmol/l, and undetectable insulin secretagogues. Use of a modified OGTT in the evaluation of the dumping syndrome is also described, as are the mixed meal test, glucagon tolerance test, c-peptide suppression test and evaluation of autoimmune hypoglycemia. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905219 | Bookshelf:NBK278985

Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family

Fetched: April 4th, 2021, 5:01am GMT by Aleksandra Gilis-Januszewska

Genes (Basel). 2021 Mar 31;12(4):512. doi: 10.3390/genes12040512.

ABSTRACT

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.

PMID:33807230 | PMC:PMC8067145 | DOI:10.3390/genes12040512

Ectopic insulinoma diagnosed by 68Ga-Exendin-4 PET/CT: A case report and review of literature

Fetched: April 1st, 2021, 5:01am GMT by Xiaona Zhang

Medicine (Baltimore). 2021 Apr 2;100(13):e25076. doi: 10.1097/MD.0000000000025076.

ABSTRACT

RATIONALE: Ectopic insulinomas are extremely rare and challenging to diagnose for clinicians. Precise preoperative localization is essential to successful treatment.

PATIENT CONCERNS: A 23-year-old man presented with a 1-year history of recurrent hypoglycemia.

DIAGNOSIS: Examinations in the local hospital did not reveal any pancreatic lesion. After admission, a fasting test and a 5-hour oral glucose tolerance test (OGTT) suggested a diagnosis of endogenous hyperinsulinemic hypoglycemia. Enhanced volume perfusion computed tomography (VPCT) revealed 2 nodules in the tail of the pancreas, a nodule in the gastric antrum, and a nodule in the hilum of the spleen. To differentiate which nodule was responsible for hypoglycemia, we performed 68Ga-Exendin-4 PET/CT and 68Ga-DOTATATE PET/CT which helped to make a conclusive diagnosis that the lesion in the gastric antrum was an ectopic insulinoma.

INTERVENTIONS: The patient was cured with minimally invasive laparoscopic resection of the tumor.

OUTCOMES: The symptoms were relieved and the blood glucose level remained normal after surgery.

CONCLUSIONS: This case shows that 68Gallium-exendin-4 PET/CT is useful for precise localization and thereby successful treatment of insulinoma, especially for occult insulinomas and those derived from an ectopic pancreas.

PMID:33787590 | PMC:PMC8021326 | DOI:10.1097/MD.0000000000025076

The appearance of canine insulinoma on dual phase computed tomographic angiography

Fetched: March 27th, 2021, 5:01am GMT by P Coss

J Small Anim Pract. 2021 Mar 26. doi: 10.1111/jsap.13336. Online ahead of print.

ABSTRACT

OBJECTIVES: To further evaluate the appearance of insulinoma in dogs on dual-phase CT angiography, given the disparity of findings in recent publications. To establish whether CT angiographic localisation of insulinoma correlates with surgical findings.

MATERIALS AND METHODS: Single centre study of dogs with a final diagnosis of insulinoma which underwent abdominal CT angiography. Scans were retrospectively re-evaluated for specific features by two board-certified veterinary radiologists. These findings were also subsequently compared to surgical and histopathological reports to determine the accuracy of lesion localisation on CT.

RESULTS: Thirty-five cases were included in final analysis, with pancreatic nodules identified in 33. Twenty-one were confirmed as insulinoma with histopathology. Jack Russell Terriers were over-represented. Twenty of 21 cases with confirmed insulinoma and 27 of 33 overall showed hyperattenuation in the arterial phase. The mean size of pancreatic insulinoma on CT was 15.1 mm, and 18.2% were larger than 20 mm. Eighteen of 21 confirmed and eight of 12 suspected insulinomas caused a deformation of the pancreatic shape, with two only identified as a result of this feature as these lesions were isoattenuating throughout the study. Pancreatic insulinoma location at surgery matched that described on the CT images in 17 of 19 cases where location was described in the surgical report.

CLINICAL SIGNIFICANCE: In contrast to recent publications, this study suggests hyperattenuation of insulinomas in the arterial phase is a predominant feature, and that hypoattenuation or isoattenuation are much less common. CT angiography is accurate in prediction of lesion location before surgery in most cases.

PMID:33769568 | DOI:10.1111/jsap.13336

Domain mapping of chondroitin/dermatan sulfate glycosaminoglycans enables structural characterization of proteoglycans

Fetched: March 25th, 2021, 5:01am GMT by Andrea Persson

Mol Cell Proteomics. 2021 Mar 20;20:100074. doi: 10.1016/j.mcpro.2021.100074. Online ahead of print.

ABSTRACT

Of all posttranslational modifications known, glycosaminoglycans (GAGs) remain one of the most challenging to study, and despite the recent years of advancement in MS technologies and bioinformatics, detailed knowledge about the complete structures of GAGs as part of proteoglycans (PGs) is limited. To address this issue, we have developed a protocol to study PG-derived GAGs. Chondroitin/dermatan sulfate conjugates from the rat insulinoma cell line, INS-1832/13, known to produce primarily the PG chromogranin-A, were enriched by anion-exchange chromatography after pronase digestion. Following benzonase and hyaluronidase digestions, included in the sample preparation due to the apparent interference from oligonucleotides and hyaluronic acid in the analysis, the GAGs were orthogonally depolymerized and analyzed using nano-flow reversed-phase LC-MS/MS in negative mode. To facilitate the data interpretation, we applied an automated LC-MS peak detection and intensity measurement via the Proteome Discoverer software. This approach effectively provided a detailed structural description of the nonreducing end, internal, and linkage region domains of the CS/DS of chromogranin-A. The copolymeric CS/DS GAGs constituted primarily consecutive glucuronic-acid-containing disaccharide units, or CS motifs, of which the N-acetylgalactosamine residues were 4-O-sulfated, interspersed by single iduronic-acid-containing disaccharide units. Our data suggest a certain heterogeneity of the GAGs due to the identification of not only CS/DS GAGs but also of GAGs entirely of CS character. The presented protocol allows for the detailed characterization of PG-derived GAGs, which may greatly increase the knowledge about GAG structures in general and eventually lead to better understanding of how GAG structures are related to biological functions.

PMID:33757834 | DOI:10.1016/j.mcpro.2021.100074

Bone marrow-derived mesenchymal stem cells improve rat islet graft revascularization by upregulating ISL1

Fetched: March 24th, 2021, 5:01am GMT by Ying Wang

Stem Cells. 2021 Mar 22. doi: 10.1002/stem.3378. Online ahead of print.

ABSTRACT

Revascularization of the islet transplant is a crucial step that defines the success rate of patient recovery. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to promote revascularization; however, the underlying cellular mechanism remains unclear. Moreover, our liquid chromatography-tandem mass spectrometry results showed that BMSCs could promote the expression of insulin gene enhancer binding protein-1 (ISL1) in islets. ISL1 is involved in islets proliferation and plays a potential regulatory role in the revascularization of islets. This study identifies the ISL1 protein as a potential modulator in BMSCs-mediated revascularization of islet grafts. We demonstrated that the survival rate and insulin secretion of islets were increased in the presence of BMSCs, indicating that BMSCs promote islet revascularization in a coculture system and rat diabetes model. Interestingly, we also observed that the presence of BMSCs led to an increase in ISL1 and vascular endothelial growth factor A (VEGFA) expression in both islets and the INS-1 rat insulinoma cell line. In silico protein structure modeling indicated that ISL1 is a transcription factor that has four binding sites with VEGFA mRNA. Further results showed that overexpression of ISL1 increased both the abundance of VEGFA transcripts and protein accumulation, while inhibition of ISL1 decreased the abundance of VEGFA. Using a ChIP-qPCR assay, we demonstrated that direct molecular interactions between ISL1 and VEGFA occur in INS-1 cells. Together, these findings reveal that BMSCs promote the expression of ISL1 in islets and lead to an increase in VEGFA in islet grafts. Hence, ISL1 is a potential target to induce early revascularization in islet transplantation.

PMID:33754392 | DOI:10.1002/stem.3378

Dimethyl sulfoxide acutely enhances regulated insulin secretion in the MIN6-K8 mouse insulinoma cell line

Fetched: March 21st, 2021, 5:01am GMT by Christopher M Carmean

Histochem Cell Biol. 2021 Mar 20. doi: 10.1007/s00418-021-01984-z. Online ahead of print.

ABSTRACT

Diabetes mellitus is a metabolic disorder projected to afflict 700 million people globally by 2045. Fundamental to the progression of diabetes is an insufficient supply of insulin to meet metabolic demand. The MIN6-K8 cell line is a mouse insulinoma model of pancreatic β-cells frequently used to study the mechanisms of insulin secretion. Here, we evaluated the effects of short-term exposure to dimethyl sulfoxide (DMSO), a polar aprotic solvent commonly used in drug screening, on physiological characteristics of MIN6-K8 cells. Short-term exposure of MIN6-K8 cells to DMSO enhanced glucose-induced and tolbutamide-stimulated insulin secretion without significant effects on basal secretion or potassium responsiveness. Calcium influx was enhanced during glucose and tolbutamide treatments, suggesting that DMSO's mechanism of action is upstream of calcium-dependent insulin granule exocytosis. Based on these studies, investigators should use caution when conducting experiments with DMSO in the MIN6-K8 cell line and should report all DMSO concentrations when used as a solvent.

PMID:33743067 | DOI:10.1007/s00418-021-01984-z

Surgery of pancreas tumors in pediatric and adolescent patients: a single institution experience in South America

Fetched: March 21st, 2021, 5:01am GMT by Oscar Paredes

Pediatr Surg Int. 2021 Mar 19. doi: 10.1007/s00383-021-04877-3. Online ahead of print.

ABSTRACT

PURPOSE: Pancreas tumors are extremely rare in pediatric and adolescent patients. Surgical resection is the mainstay of treatment; however, the data are limited with respect to morbidity and mortality. We aimed to evaluate short- and long-term outcomes of pediatric and adolescent patients who underwent surgical resection of pancreatic tumors.

METHODS: Patients [Formula: see text] 18-year-olds who underwent resection of pancreas tumor at the National Institute of Neoplastic Diseases INEN during 2000-2020 were included.

RESULTS: Thirty-four patients were diagnosed; 28 patients were female and 6 were male. The median age was 13.4-years-old. Histological diagnosis was solid pseudopapillary neoplasm (SPN) (n = 29, 85.3%), pancreatoblastoma (n = 3), neuroendocrine carcinoma (n = 1), and insulinoma (n = 1). No patient experienced postoperative mortality and 15 (44.1%) patients developed postoperative complications including pancreatic fistula as the most frequent. Under a median follow-up period of 33.8 (0.5-138) months, four (11.8%) patients died. Of the 29 patients with SPN, the 3- and-5-year OS rates were 100% and 83.1%, respectively.

CONCLUSIONS: SPN was the most frequent cause of surgical treatment for pediatric and adolescent patients in the high-volume cancer center in Peru and was associated with favorable survival. Pancreaticoduodenectomy was safely performed in this patient group with acceptable morbidity and zero mortality.

PMID:33742268 | DOI:10.1007/s00383-021-04877-3

Islet neogenesis associated protein (INGAP) protects pancreatic β cells from IL-1β and IFNγ-induced apoptosis

Fetched: March 19th, 2021, 5:01am GMT by Eni Nano

Cell Death Discov. 2021 Mar 17;7(1):56. doi: 10.1038/s41420-021-00441-z.

ABSTRACT

The goal of this study was to determine whether recombinant Islet NeoGenesis Associated Protein (rINGAP) and its active core, a pentadecapeptide INGAP^104-118 (Ingap-p), protect β cells against cytokine-induced death. INGAP has been shown to induce islet neogenesis in diabetic animals, to stimulate β-cell proliferation and differentiation, and to improve islet survival and function. Importantly, Ingap-p has shown promising results in clinical trials for diabetes (phase I/II). However, the full potential of INGAP and its mechanisms of action remain poorly understood. Using rat insulinoma cells RINm5F and INS-1 treated with interleukin-1β (IL-1β) and interferon-gamma (IFN-γ), we demonstrate here that both rINGAP and Ingap-p inhibit apoptosis, Caspase-3 activation, inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and explore the related signaling pathways. As expected, IL-1β induced nuclear factor kappa B (NF-κB), p38, and JNK signaling, whereas interferon-gamma (IFN-γ) activated the JAK2/STAT1 pathway and potentiated the IL-1β effects. Both rINGAP and Ingap-p decreased phosphorylation of IKKα/β, IkBα, and p65, although p65 nuclear translocation was not inhibited. rINGAP, used for further analysis, also inhibited STAT3, p38, and JNK activation. Interestingly, all inhibitory effects of rINGAP were observed for the cytokine cocktail, not IL-1β alone, and were roughly equal to reversing the potentiating effects of INFγ. Furthermore, rINGAP had no effect on IL-1β/NF-κB-induced gene expression (e.g., Ccl2, Sod2) but downregulated several IFNγ-stimulated (Irf1, Socs1, Socs3) or IFNγ-potentiated (Nos2) genes. This, however, was observed again only for the cytokine cocktail, not IFNγ alone, and rINGAP did not inhibit the IFNγ-induced JAK2/STAT1 activation. Together, these intriguing results suggest that INGAP does not target either IL-1β or IFNγ individually but rather inhibits the signaling crosstalk between the two, the exact mechanism of which remains to be investigated. In summary, our study characterizes the anti-inflammatory effects of INGAP, both protein and peptide, and suggests a new therapeutic utility for INGAP in the treatment of diabetes.

PMID:33731692 | PMC:PMC7969959 | DOI:10.1038/s41420-021-00441-z

CGM for insulinoma screening: a prospective and observational case-control study

Fetched: March 18th, 2021, 5:02am GMT by Jingyuan Ma

Endocr Relat Cancer. 2021 May;28(5):291-300. doi: 10.1530/ERC-20-0447.

ABSTRACT

Insulin release index (IRI) based on 72-h fasting test has been used for the definitive diagnosis of insulinoma; however, hospitalization and subsequent costs contribute to the disadvantage of IRI. Therefore, a simple and cost-effective screening procedure for the diagnosis of insulinoma for outpatients are crucially needed. Continuous glucose monitoring (CGM) has been widely used for monitoring high level of glucose in diabetic patients. The aim of the study is to determine the potential contribution or implementation of CGM in the screening of the insulinoma. We performed a single-center prospective study with the demographics and laboratory data including 28 patients with the pathological diagnosis of insulinoma and 25 patients with functional hypoglycemia as control group. The analysis showed that areas under the receiver operating characteristic (ROC) curve of coefficient of variation (CV) was 0.914. The CV cutoff point was 19% with the Youden 62.1%, the corresponding sensitivity and specificity were 82.1 and 80%, respectively. In patients with CV greater than the median, more than 60% of insulinomas were located in the head of the pancreas; most Ki-67 values were more than 2% and when compared with the group with CV smaller than the median, the average tumor size was 2.7 times larger. In conclusion, CGM can be used as a valuable tool in not only monitoring high glucose levels in diabetic patients but also identifying the etiology of insulinoma. CV greater than 19% can be highly effective for the screening of insulinoma in outpatients.

PMID:33729991 | DOI:10.1530/ERC-20-0447

Clinical findings, neurological manifestations and survival of dogs with insulinoma: 116 cases (2009-2020)

Fetched: March 17th, 2021, 5:03am GMT by D Ryan

J Small Anim Pract. 2021 Mar 16. doi: 10.1111/jsap.13318. Online ahead of print.

ABSTRACT

OBJECTIVES: To review the clinical findings and outcome in dogs diagnosed with insulinoma, and to assess which factors are predictors of overall survival. Additionally, to describe the neurological manifestations of this population and their correlation with survival.

MATERIALS AND METHODS: Retrospective multicentric study of canine insulinoma cases (2009 to 2020). Signalment, clinical history, neurological examination, diagnostic findings, treatment and outcome were obtained from clinical records. Univariate and multivariate analyses were used to compare the overall survival.

RESULTS: One hundred and sixteen cases were included. Median duration of clinical signs before presentation was 1.5 months. The most common presenting clinical signs were weakness (59.5%), epileptic seizures (33.6%) and changes in consciousness or behaviour (27.6%). Three dogs were suspected to have paroxysmal dyskinesia. Thirty-two dogs had an abnormal neurological examination, most commonly showing obtundation (28.1%), decreased withdrawal reflexes (21.9%) and absent menace response (18.8%). Overall survival for dogs undergoing surgery (20 months) was significantly longer than in medically treated (8 months; adjusted hazard ratio: 0.33; 95% confidence interval: 0.18, 0.59). Presence of metastases was the only other variable associated with prognosis (adjusted hazard ratio 1.72; 95% confidence interval: 1.02, 2.91).

CLINICAL SIGNIFICANCE: Clinical signs of canine insulinoma are vague and non-specific. Weakness, epileptic seizures and changes in mentation or behaviour were the most commonly reported. Obtunded mentation and forebrain neurolocalisation were the main neurological manifestations. Dogs undergoing surgery had a longer overall survival compared to medically treated cases, and dogs with metastasis had a shorter overall survival regardless of treatment modality. Abnormalities in the neurological examination did not correlate with prognosis.

PMID:33724496 | DOI:10.1111/jsap.13318

Pancreatic proinsulinoma

Fetched: March 13th, 2021, 5:01am GMT by A G Kriger

Khirurgiia (Mosk). 2021;(3):5-10. doi: 10.17116/hirurgia20210315.

ABSTRACT

OBJECTIVE: To report own experience in the treatment of patients with proinsulinoma.

MATERIAL AND METHODS: There were 10 patients with increased proinsulin production and normal insulin level since 2017. Most of them were young women.

RESULTS: Fasting hypoglycemia in all patients was severe (up to 0.7 mmol/l). Clinical picture consisted of typical symptoms similar to those in insulinoma. The main difference in the course of proinsulinoma was the absence of weight gain in 7 patients and rapid weight loss (from 210 to 90 kg within 9 months) in 1 patient. All patients with proinsulinoma underwent surgery. In most cases, minimally aggressive surgery was performed.

CONCLUSION: Proinsulinoma is an extremely rare endocrine-active neuroendocrine pancreatic tumor. Differential features of proinsulinoma are the absence of weight gain and normal insulin levels in the presence of hypoglycemia. Surgery is the only radical method of treatment.

PMID:33710820 | DOI:10.17116/hirurgia20210315

Frequencies of CD8 and DN MAIT Cells Among Children Diagnosed With Type 1 Diabetes Are Similar to Age-Matched Controls

Fetched: March 13th, 2021, 5:01am GMT by Robert Z Harms

Front Immunol. 2021 Feb 23;12:604157. doi: 10.3389/fimmu.2021.604157. eCollection 2021.

ABSTRACT

Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) from age-matched T1D and control children using flow cytometry. We observed that CD8 and DN MAIT cell frequencies were similarly abundant between the two groups. We tested for associations between MAIT cell frequency and T1D-associated parameters, which could reveal a pathogenic role for MAIT cells in the absence of changes in frequency. We found no significant associations between CD8 and DN MAIT cell frequency and levels of islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65) autoantibodies, zinc transporter 8 (ZNT8) autoantibodies, and insulinoma antigen 2 (IA-2) autoantibodies. Furthermore, CD8 and DN MAIT cell frequencies were not significantly associated with time since diagnosis, c-peptide levels, HbA1c, and BMI. As we have examined this cohort for multiple soluble factors previously, we tested for associations between relevant factors and MAIT cell frequency. These could help to explain the broad range of MAIT frequencies we observed and/or indicate disease-associated processes. Although we found nothing disease-specific, we observed that levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were all associated with MAIT cell frequency. Finally, previous cytomegalovirus infection was associated with reduced CD8 and DN MAIT cells. From this evaluation, we found no connections between CD8 and DN MAIT cells and children with T1D. However, we did observe several intrinsic and extrinsic factors that could influence peripheral MAIT cell abundance among all children. These factors may be worth consideration in future experimental design.

PMID:33708202 | PMC:PMC7940386 | DOI:10.3389/fimmu.2021.604157

Mutation and Expression of Gene YY1 in Pancreatic Neuroendocrine Tumors and its Clinical Significance

Fetched: March 13th, 2021, 5:01am GMT by Yu-Li Song

Endocr Pract. 2021 Mar 9:S1530-891X(21)00080-X. doi: 10.1016/j.eprac.2021.02.016. Online ahead of print.

ABSTRACT

OBJECTIVE: The clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs.

METHODS: A total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features.

RESULTS: A recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis.

CONCLUSION: The hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.

PMID:33705973 | DOI:10.1016/j.eprac.2021.02.016

Lin28a ameliorates glucotoxicity-induced beta cell dysfunction and apoptosis

Fetched: March 12th, 2021, 5:01am GMT by Kyeong-Min Lee

BMB Rep. 2021 Apr;54(4):215-220. doi: 10.5483/BMBRep.2021.54.4.255.

ABSTRACT

An excessive and prolonged increase in glucose levels causes β-cell dysregulation, which is accompanied by impaired insulin synthesis and secretion, a condition known as glucotoxicity. Although it is known that both Lin28a and Lin28b regulate glucose metabolism, other molecular mechanisms that may protect against glucotoxicity are poorly understood. We investigated whether Lin28a overexpression can improve glucotoxicityinduced β-cell dysregulation in INS-1 and primary rat islet cells. INS-1, a rat insulinoma cell line was cultured and primary rat islet cells were isolated from SD-rats. To define the effect of Lin28a in chronic high glucose-induced β-cell dysregulation, we performed several in vitro and ex-vivo experiments. Chronic exposure to high glucose led to a downregulation of Lin28a mRNA and protein expression, followed by a decrease in insulin mRNA expression and secretion in β-cells. The mRNA and protein expression levels of PDX-1 and BETA2, were reduced; The levels of apoptotic factors, including c-caspase3 and the Bax/Bcl-2 ratio, were increased due to glucotoxicity. Adenovirusmediated Lin28a overexpression in β-cells reversed the glucotoxicity- induced reduction of insulin secretion and insulin mRNA expression via regulation of β-cell-enriched transcription factors such as PDX-1 and BETA2. Adenovirus-mediated overexpression of Lin28a downregulated the glucotoxicity-induced upregulation of c-caspase3 levels and the Bax/Bcl-2 ratio, while inhibition of endogenous Lin28a by small interfering RNA resulted in their up-regulation. Lin28a counteracted glucotoxicity-induced downregulation of p-Akt and p-mTOR. Our results suggest that Lin28a protects pancreatic β-cells from glucotoxicity through inhibition of apoptotic factors via the PI3 kinase/Akt/mTOR pathway. [BMB Reports 2021; 54(4): 215-220].

PMID:33691905 | PMC:PMC8093937 | DOI:10.5483/BMBRep.2021.54.4.255

Feasibility of a scale-down production of [68Ga]Ga-NODAGA-Exendin-4 in a hospital based radiopharmacy

Fetched: March 11th, 2021, 5:01am GMT by Silvia Migliari

Curr Radiopharm. 2021 Mar 9. doi: 10.2174/1874471014666210309151930. Online ahead of print.

ABSTRACT

BACKGROUND: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in β-cells, but it is highly expressed in human insulinomas and gastrinomas. Several GLP-1 receptor-avid radioligands have been developed to image insulin-secreting tumors or to provide a quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4 is a high affinity ligand of the GLP1-R, which is a candidate for being labeled with a PET isotope and used for imaging purposes.

OBJECTIVE: Here, we report the development and validation results of a semi manual procedure to label [Lys40,Nle14(Ahx-NODAGA)NH2]exendin-4, with Ga-68.

METHODS: A ⁶⁸Ge/⁶⁸Ga Generator (GalliaPharma®,Eckert and Ziegler) was eluted with 0.1M HCl on an automated synthesis module (Scintomics GRP®). The peptide contained in the kit vial (Radioisotope Center POLATOM) in different amounts (10-20-30 µg) was reconstituted with 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethansulfonic acid (HEPES) solution and 68GaCl3 (400-900 MBq), followed by 10 min incubation at 95°C. The reaction solution was then purified through an Oasis HLB column. The radiopharmaceutical product was tested for quality controls (CQs), in accordance with the European Pharmacopoeia standards.

RESULTS: The synthesis of ⁶⁸Ga]Ga-NODAGA-Exendin-4 provided optimal results with 10 µg of peptide, getting the best radiochemical yield (23.53 ± 2.4 %), molar activity (100 GBq/µmol) and radiochemical purity (91.69 %).

CONCLUSION: The study developed an imaging tool [⁶⁸Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.

PMID:33687908 | DOI:10.2174/1874471014666210309151930

Averaging Strategy to Form the Imaging for Routine Reading of Insulinoma from Pancreatic Perfusion Dataset

Fetched: March 6th, 2021, 5:01am GMT by Juan Li

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2021 Feb 28;43(1):47-52. doi: 10.3881/j.issn.1000-503X.12280.

ABSTRACT

Objective To determine the appropriate averaging strategy for pancreatic perfusion datasets to create images for routine reading of insulinoma.Methods Thirty-nine patients undergoing pancreatic perfusion CT in Peking Union Medical College Hospital and diagnosed as insulinoma by pathology were enrolled in this retrospective study.The time-density curve of abdominal aorta calculated by software dynamic angio was used to decide the timings for averaging.Five strategies,by averaging 3,5,7,9 and 11 dynamic scans in perfusion,all including peak enhancement of the abdominal aorta,were investigated in the study.The image noise,pancreas signal-to-noise ratio(SNR),lesion contrast and lesion contrast-to-noise ratio(CNR)were recorded and compared.Besides,overall image quality and insulinoma depiction were also compared.ANOVA and Friedman's test were performed.Results The image noise decreased and the SNR of pancreas increased with the increase in averaging time points(all P<0.001).The lesion contrast(69.81±41.35)averaged from 5 scans showed no significant difference compared with that(72.77±45.25)averaged from 3 scans(P=0.103),both of which were higher than that in other groups(all P≤0.001).The lesion CNRs of the last four groups showed no significant difference(all P>0.99)and were higher than that of the first group(all P<0.05).There was no significant difference in overall image quality among the 5 groups(P=0.977).Conclusions Image averaged from 5 scans showed moderate image noise,pancreas SNR and relatively high lesion contrast and lesion CNR.Therefore,it is advised to be used in image averaging to detect insulinoma.

PMID:33663662 | DOI:10.3881/j.issn.1000-503X.12280

Insulinoma: A Recurrent Pancreatic Tumor Amendable to Computed Tomography-Guided Ethanol-Lipiodol Injection

Fetched: March 4th, 2021, 5:01am GMT by Himesh B Zaver

ACG Case Rep J. 2021 Feb 26;8(2):e00539. doi: 10.14309/crj.0000000000000539. eCollection 2021 Feb.

ABSTRACT

Insulinomas are rare, with an annual incidence of 1-4 people per mission. Insulinomas are the most common functioning endocrine neoplams of the pancreas. Endoscopic ultrasound has both diagnostic and therapeutic yield in undifferentiated pancreatic tumors. We present a case of a recurrent insulinoma, refractory to surgical and medical management diagnosed with endoscopic ultrasound. Our case uniquely conveys a successful, alternative approach to addressing symptomatic insulinomas refractory to surgical or medical management through computed tomography-guided percutaneous ethanol-lipiodol injection.

PMID:33654702 | PMC:PMC7909311 | DOI:10.14309/crj.0000000000000539

The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets

Fetched: March 4th, 2021, 5:01am GMT by Mariano F Zacarías-Fluck

Life Sci Alliance. 2021 Mar 2;4(5):e201900490. doi: 10.26508/lsa.201900490. Print 2021 May.

ABSTRACT

The huge cadre of genes regulated by Myc has obstructed the identification of critical effectors that are essential for Myc-driven tumorigenesis. Here, we describe how only the lack of the receptor Fzd9, previously identified as a Myc transcriptional target, impairs sustained tumor expansion and β-cell dedifferentiation in a mouse model of Myc-driven insulinoma, allows pancreatic islets to maintain their physiological structure and affects Myc-related global gene expression. Importantly, Wnt signaling inhibition in Fzd9-competent mice largely recapitulates the suppression of proliferation caused by Fzd9 deficiency upon Myc activation. Together, our results indicate that the Wnt signaling receptor Fzd9 is essential for Myc-induced tumorigenesis in pancreatic islets.

PMID:33653688 | PMC:PMC8008953 | DOI:10.26508/lsa.201900490

Diagnostic Utility of INSM1 in Medullary Thyroid Carcinoma

Fetched: March 3rd, 2021, 5:03am GMT by Jae Yeon Seok

Int J Surg Pathol. 2021 Mar 2:1066896921995935. doi: 10.1177/1066896921995935. Online ahead of print.

ABSTRACT

Insulinoma-associated protein 1 (INSM1) is shown to be an excellent marker for neuroendocrine differentiation. However, the diagnostic utility of INSM1 in medullary thyroid carcinoma (MTC) has not yet been extensively investigated. INSM1 staining was performed on 21 MTCs, 7 MTC mimickers (including 3 papillary carcinomas, 2 poorly differentiated carcinomas, 1 follicular adenoma, and 1 nodular plasma cell hyperplasia), and 3 cases of C-cell hyperplasia. INSM1 staining of these cases was compared with the traditional MTC markers including calcitonin (CT), monoclonal carcinoembryonic antigen (mCEA), chromogranin A (CgA), and synaptophysin (Syn). The H-score was generated using the QuPath program, an open-source image analysis software. All 21 MTC cases and 3 C-cell hyperplasia cases were positive for all markers. The MTC mimickers were entirely negative for INSM1. INSM1 and Syn displayed, more consistently, high expression with minimal variability than CgA that showed a wide range of expression with significant variability. mCEA and CT exhibited mostly a high expression with some variability. Being a nuclear stain, interpretation was easier with INSM1 compared to other cytoplasmic markers. INSM1 is an excellent marker for neuroendocrine differentiation, entirely applicable in the diagnosis of MTC and C-cell hyperplasia with high sensitivity and specificity. In comparison with the traditional MTC markers, INSM1 is unique in the crisp nuclear staining pattern with a consistent, diffuse, and strong expression. INSM1 can be potentially combined with CT or mCEA as a dual stain, especially when the lesional tissue is limited for a panel of immunostains.

PMID:33650906 | DOI:10.1177/1066896921995935

FoxA2 and RNA Pol II Mediate Human Islet Amyloid Polypeptide Turnover in ER-stressed Pancreatic β-cells

Fetched: March 3rd, 2021, 5:03am GMT by Diti Chatterjee Bhowmick

Biochem J. 2021 Mar 26;478(6):1261-1282. doi: 10.1042/BCJ20200984.

ABSTRACT

Here, we investigated transcriptional and trafficking mechanisms of human islet amyloid polypeptide (hIAPP) in normal and stressed β-cells. In high glucose-challenged human islets and rat insulinoma cells overexpressing hIAPP, cell fractionation studies revealed increased accumulation of hIAPP. Unexpectedly, a significant fraction (up to 22%) of hIAPP was found in the nuclear soluble and chromatin-enriched fractions of cultured human islet and rat insulinoma cells. The nucleolar accumulation of monomeric forms of hIAPP did not have any adverse effect on the proliferation of β-cells nor did it affect nucleolar organization or function. However, intact nucleolar organization and function were essential for hIAPP expression under normal and ER-stress conditions as RNA polymerase II inhibitor, α-amanitin, reduced hIAPP protein expression evoked by high glucose and thapsigargin. Promoter activity studies revealed the essential role of transcription factor FoxA2 in hIAPP promoter activation in ER-stressed β-cells. Transcriptome and secretory studies demonstrate that the biosynthetic and secretory capacity of islet β-cells was preserved during ER stress. Thus, the main reason for increased intracellular hIAPP accumulation is its enhanced biosynthesis under these adverse conditions.

PMID:33650632 | PMC:PMC8011634 | DOI:10.1042/BCJ20200984

Permalink for 'Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study'

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study

Fetched: March 3rd, 2021, 5:03am GMT by Nicolas Santucci

World J Surg. 2021 Jun;45(6):1794-1802. doi: 10.1007/s00268-021-06005-7. Epub 2021 Mar 1.

ABSTRACT

AIM: To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs).

BACKGROUND: The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense.

METHODS: Thirty-one MEN1 patients from the Groupe d'étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed.

RESULTS: Indication for surgery was: Zollinger-Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0-433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13-110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8-98.3] and ten-year overall survival was 89.1% [CI 69.6-96.4]. After a mean follow-up of 151 months (range 0-433), the biochemical cure rate for MEN-1 related gastrinomas was 61%.

CONCLUSION: In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.

PMID:33649917 | PMC:PMC8093175 | DOI:10.1007/s00268-021-06005-7

Management Impact of 68Ga-DOTATATE PET/CT in Neuroendocrine Tumors

Fetched: March 2nd, 2021, 5:03am GMT by Redmond-Craig Anderson

Nucl Med Mol Imaging. 2021 Feb;55(1):31-37. doi: 10.1007/s13139-020-00677-0. Epub 2021 Jan 7.

ABSTRACT

PURPOSE: The goal of our retrospective single tertiary academic medical center investigation was to examine the added diagnostic value and clinical impact of ⁶⁸Ga-DOTATATE PET/CT in the therapeutic management of patients with neuroendocrine tumors (NETs).

METHODS: Imaging database was queried for all "PET-DOTATATE" examinations performed at our tertiary care academic institution using MONTAGE™. The patient's clinical history and recent prior imaging were reviewed. The additional diagnostic value and clinical management impact of ⁶⁸Ga-DOTATATE were assessed through retrospective chart review.

RESULTS: A total of 81 ⁶⁸Ga-DOTATATE PET/CT scans in 74 patients were found, and 11 patients were excluded from analysis as they had no prior imaging available for comparison, with resultant analysis cohort of 63 patients. Six patients had 2 or more ⁶⁸Ga-DOTATATE PET/CT examinations. The most common primary diagnosis was undifferentiated NET (63.5%), followed by carcinoid (27.0%), paraganglioma (4.8%), insulinoma (3.2%), and pheochromocytoma (1.6%). The primary sites of disease from the most to the least common were the pancreas (36.5%), small bowel (22.2%), unknown primary (15.9%), lung (6.3%), large bowel (6.3%), and mesentery (4.8%), and other locations accounted for 7.9%. In patients who had prior imaging available for comparison, there were new lesions identified on ⁶⁸Ga-DOTATATE PET/CT in 21 patients (33.3%) that were not identified on other prior imaging modalities. Of these patients, 5 underwent subsequent MRI and 1 had a repeat ⁶⁸Ga-DOTATATE PET/CT to further characterize new lesions seen. Moreover, 15 patients (23.8%) had a change in treatment plan, including altering medical therapy in 9 patients, change in planned extent of surgical management in 5 patients, and cancelation of a planned primary tumor resection in 1 patient with metastatic disease.

CONCLUSION: Our retrospective cohort demonstrated that ⁶⁸Ga-DOTATATE PET/CT improves lesion detection over conventional imaging in 33.3% and impacts the therapeutic management in 23.8% of patients with NET.

PMID:33643487 | PMC:PMC7881063 | DOI:10.1007/s13139-020-00677-0

Insulinoma in tuberous sclerosis: An entity not to be missed

Fetched: February 27th, 2021, 5:02am GMT by Mohammed S Al Qahtani

Saudi Med J. 2021 Mar;42(3):332-337. doi: 10.15537/smj.2021.42.3.20200490.

ABSTRACT

Pancreatic neuroendocrine tumors are rare with an incident rate of 5 cases per million individuals. Tuberous sclerosis complex is an autosomal dominant disease. This disease involves multisystem and occurs in one out of every 6,000-10,000 individuals. In this study, we describe a 47-year-old male known tuberous sclerosis patient with an insulinoma. The tumor was incidentally detected in follow-up imaging for a previous ampulla of Vater tubular adenoma. However, the patient reported symptoms of hypoglycemia. The insulinoma was enucleated successfully. Histopathology revealed a well-differentiated, grade one neuroendocrine tumor measuring around 2 cm in diameter. Seven cases were reported in the literature of tuberous sclerosis-associated insulinoma. The 7 reported cases had different hypoglycemia related symptoms. The reported tumors varied in size and location on the pancreas. This paper details the eighth case worldwide where an insulinoma occurred in a tuberous sclerosis patient.

PMID:33632913 | DOI:10.15537/smj.2021.42.3.20200490

INSM1 Expression in Chordomas

Fetched: February 26th, 2021, 5:02am GMT by Maroa Dridi

Am J Clin Pathol. 2021 Feb 25:aqaa250. doi: 10.1093/ajcp/aqaa250. Online ahead of print.

ABSTRACT

OBJECTIVES: Chordomas are rare malignant tumors with a broad differential diagnosis, including chondrosarcomas and metastatic carcinomas. Recently, insulinoma-associated protein 1 (INSM1) has gained great interest regarding the diagnosis of neuroendocrine tumors but also extraskeletal myxoid chondrosarcomas. However, its expression in chordomas remains largely unknown.

METHODS: We retrospectively examined 57 chordomas for INSM1 expression.

RESULTS: INSM1 expression was found in only 5% of tumors.

CONCLUSIONS: This marker is rarely expressed in this type of tumor, raising questions about neuroendocrine differentiation.

PMID:33629710 | DOI:10.1093/ajcp/aqaa250

The many lives of Myc in the pancreatic β-cell

Fetched: February 24th, 2021, 5:01am GMT by Carolina Rosselot

J Biol Chem. 2020 Dec 2;296:100122. doi: 10.1074/jbc.REV120.011149. Online ahead of print.

ABSTRACT

Diabetes results from insufficient numbers of functional pancreatic β-cells. Thus, increasing the number of available functional β-cells ex vivo for transplantation, or regenerating them in situ in diabetic patients, is a major focus of diabetes research. The transcription factor, Myc, discovered decades ago lies at the nexus of most, if not all, known proliferative pathways. Based on this, many studies in the 1990s and early 2000s explored the potential of harnessing Myc expression to expand β-cells for diabetes treatment. Nearly all these studies in β-cells used pathophysiological or supraphysiological levels of Myc and reported enhanced β-cell death, dedifferentiation, or the formation of insulinomas if cooverexpressed with Bcl-xL, an inhibitor of apoptosis. This obviously reduced the enthusiasm for Myc as a therapeutic target for β-cell regeneration. However, recent studies indicate that "gentle" induction of Myc expression enhances β-cell replication without induction of cell death or loss of insulin secretion, suggesting that appropriate levels of Myc could have therapeutic potential for β-cell regeneration. Furthermore, although it has been known for decades that Myc is induced by glucose in β-cells, very little is known about how this essential anabolic transcription factor perceives and responds to nutrients and increased insulin demand in vivo. Here we summarize the previous and recent knowledge of Myc in the β-cell, its potential for β-cell regeneration, and its physiological importance for neonatal and adaptive β-cell expansion.

PMID:33460934 | DOI:10.1074/jbc.REV120.011149

Hypoglycemia in non -diabetic patients

Fetched: February 24th, 2021, 5:01am GMT by Jan Škrha

Vnitr Lek. 2020 Fall;66(7):447-448.

ABSTRACT

Hypoglycemia is a rather frequent complication of diabetes treatment, however it can occur also in non-diabetic patients. The article presents a brief differential diagnosis of hypoglycemia in non-diabetic patients.

PMID:33380125

Pancreatic neuroendocrine tumors: Surgical outcomes and survival analysis

Fetched: February 24th, 2021, 5:01am GMT by Joseph N Fahmy

Am J Surg. 2020 Dec 24:S0002-9610(20)30815-1. doi: 10.1016/j.amjsurg.2020.12.037. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic neuroendocrine tumors are rare, with rising incidence and limited clinicopathological studies.

METHODS: Adult patients with pNET at a single tertiary care center were retrospectively evaluated.

RESULTS: In total, 87 patients with histologically confirmed pNET who underwent resection were evaluated. 11% of patients had functioning pNETs: 9 insulinoma and 1 VIPoma. The majority (88.5%) were nonfunctioning. The most common surgical procedure performed was distal pancreatectomy with splenectomy (36.8%). 35.6% of cases were performed with minimally invasive surgery (MIS). MIS patients had fewer postoperative complications, shorter length of stay, and fewer ICU admissions.Disease-free survival (DFS) was unaffected by tumor size (p = 0.5) or lymph node status (p = 0.62). Patients with high-grade (G3) tumors experienced significantly shorter DFS (p = 0.02).

CONCLUSIONS: This series demonstrates that survival in patients with pNET is driven mostly by tumor grade, though overall most have long-term survival after surgical resection. Additionally, an MIS approach is efficacious in appropriately selected cases.

PMID:33375953 | DOI:10.1016/j.amjsurg.2020.12.037

Permalink for 'Thymic Carcinoid as the First Manifestation of Multiple Endocrine Neoplasia Type 1 Syndrome: A Case Report and Review of the Literature'

Thymic Carcinoid as the First Manifestation of Multiple Endocrine Neoplasia Type 1 Syndrome: A Case Report and Review of the Literature

Fetched: February 24th, 2021, 5:01am GMT by Meiling Zheng

Ann Clin Lab Sci. 2020 Nov;50(6):825-833.

ABSTRACT

The present study reported a rare case with thymic carcinoid as the first manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome, which presented with gene mutations of the MEN1 and glucokinase regulatory protein (GCKR). In this report, a 40-year-old male was diagnosed as MEN1 syndrome with thymic carcinoid, pancreatic cancer, hyperparathyroidism, and insulinoma with intrahepatic metastasis. Genetic testing showed the mutations of the MEN1 (c.378 G>A, p. Trp126*) in the patient, his children and two sisters, and GCKR (c.151C>T, p. Arg51*) gene in the patient and his children. The pathological examination showed that neuroendocrine tumor (NET) of the pancreas was characterized as 6 mitoses per 10 high-power fields (HPF), infiltration of adipose tissue, no intravascular tumor thrombus and nerve infiltration. In addition, NET of the liver was characterized as 4 mitoses per 10 HPF, no intravascular tumor thrombus and nerve infiltration. Immunohistochemical staining showed Ckpan (+), Syn (+), CgA (+), CD 56 (+), PGP 9.5 (+), and Ki67-positive cells (8-10%) in NET. Therefore, we suggested that genetic testing in family members of MEN1 patient, which may be helpful for early diagnosis.

PMID:33334800

Somatostatin analogues for the treatment of hyperinsulinaemic hypoglycaemia

Fetched: February 24th, 2021, 5:01am GMT by Basma Haris

Ther Adv Endocrinol Metab. 2020 Dec 2;11:2042018820965068. doi: 10.1177/2042018820965068. eCollection 2020.

ABSTRACT

Hyperinsulinaemic hypoglycaemia (HH) is a biochemical finding of low blood glucose levels due to the dysregulation of insulin secretion from pancreatic β-cells. Under normal physiological conditions, glucose metabolism is coupled to β-cell insulin secretion so that blood glucose levels are maintained within the physiological range of 3.5-5.5 mmol/L. However, in HH this coupling of glucose metabolism to insulin secretion is perturbed so that insulin secretion becomes unregulated. HH typically occurs in the neonatal, infancy and childhood periods and can be due to many different causes. Adults can also present with HH but the causes in adults tend to be different. Somatostatin (SST) is a peptide hormone that is released by the delta cells (δ-cells) in the pancreas. It binds to G protein-coupled SST receptors to regulate a variety of location-specific and selective functions such as hormone inhibition, neurotransmission and cell proliferation. SST plays a potent role in the regulation of both insulin and glucagon secretion in response to changes in glucose levels by negative feedback mechanism. The half-life of SST is only 1-3 min due to quick degradation by peptidases in plasma and tissues. Thus, a direct continuous intravenous or subcutaneous infusion is required to achieve the therapeutic effect. These limitations prompted the discovery of SST analogues such as octreotide and lanreotide, which have longer half-lives and therefore can be administered as injections. SST analogues are used to treat different forms of HH in children and adults and therapeutic effect is achieved by suppressing insulin secretion from pancreatic β-cells by complex mechanisms. These treatments are associated with several side effects, especially in the newborn period, with necrotizing enterocolitis being the most serious side effect and hence SS analogues should be used with extreme caution in this age group.

PMID:33329885 | PMC:PMC7720331 | DOI:10.1177/2042018820965068

Permalink for 'Vitamin D Rescues Pancreatic β Cell Dysfunction due to Iron Overload via Elevation of the Vitamin D Receptor and Maintenance of Ca2+ Homeostasis'

Vitamin D Rescues Pancreatic β Cell Dysfunction due to Iron Overload via Elevation of the Vitamin D Receptor and Maintenance of Ca2+ Homeostasis

Fetched: February 24th, 2021, 5:01am GMT by Yoo Jeong Lee

Mol Nutr Food Res. 2021 Feb;65(4):e2000772. doi: 10.1002/mnfr.202000772. Epub 2021 Jan 15.

ABSTRACT

SCOPE: Accumulating evidence indicates that micronutrients are related to metabolic diseases. However, comparatively less attention has been devoted to their influence on each other during the development of metabolic diseases. To investigate the underlying mechanisms, the effects of iron and vitamin D on pancreatic β cell functions are examined.

METHODS AND RESULTS: Iron overload is induced in INS-1 rat insulinoma pancreatic β cells and it is found that iron overload dramatically reduce expression of the vitamin D receptor (VDR). Iron overload-induced β cell dysfunction is rescued by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) cotreatment via restoration of VDR level and the consequent maintenance of Ca²⁺ homeostasis. Iron accumulation is also observed in the islets of 22-month-old C57BL/6 mice fed with a chow diet (1000 IU vitamin D3 per kg). In contrast, islet iron accumulation and hyperinsulinemia are ameliorated in mice fed with a vitamin D3 -supplemented diet (20 000 IU kg^-1 ).

CONCLUSION: The authors show that functional failure of β cells due to iron accumulation is rescued by 1,25(OH)2 D3 , and iron overload significantly reduces VDR levels in β cells. These results suggest that iron and vitamin D inversely influence pancreatic β cell function.

PMID:33325123 | DOI:10.1002/mnfr.202000772

Permalink for 'Insulinoma-associated Protein 1 Expression and Its Diagnostic Significance in Female Genital Tract Neuroendocrine Carcinomas'

Insulinoma-associated Protein 1 Expression and Its Diagnostic Significance in Female Genital Tract Neuroendocrine Carcinomas

Fetched: February 24th, 2021, 5:01am GMT by Ching-Heng Ting

Int J Gynecol Pathol. 2020 Dec 14. doi: 10.1097/PGP.0000000000000722. Online ahead of print.

ABSTRACT

Neuroendocrine carcinomas (NECs) are rare, but aggressive malignant tumors of female genital tract, especially in uterine the cervix. Beside histologic morphology, positivity of neuroendocrine markers with immunohistochemistry plays an important role in diagnosis of NECs. Insulinoma-associated protein 1 (INSM1) is a novel marker reported to be widely expressed in a variety of neuroendocrine tumors. A previous study also suggested INSM1 has superior performance to conventional neuroendocrine markers in cervical NECs. In our present study, comparison between immunomarkers was performed in female genital tract NECs. Forty-nine patients with gynecologic NECs (4 vagina, 39 cervix, 5 endometrium, 1 ovary) were included from 1993 to 2019 at our center. Immunohistochemistry was performed with INSM1, CD56, synaptophysin (SYN), chromogranin-A (CgA), and thyroid transcription factor 1 (TTF1). The results show INSM1 has superior sensitivity and intensity compared with CD56, SYN, CgA, and TTF1 in cervical small cell NECs, but not in large cell NECs. In contrast to cervical NECs, INSM1 immunohistochemistry shows only focal and weak staining in endometrial NECs. Our result suggested INSM1 is a sensitive marker which can be used as first-line test in histologic suspicious cervical cases, especially small cell NECs. However, negative INSM1 stain does not exclude the possibility of NECs. In endometrial NECs, conventional panel with CD56, SYN, CgA has better diagnostic performance than INSM1 alone.

PMID:33323849 | DOI:10.1097/PGP.0000000000000722

Evaluation for type 1 diabetes associated autoantibodies in diabetic and non-diabetic Australian terriers and Samoyeds

Fetched: February 24th, 2021, 5:01am GMT by Allison L O'Kell

Canine Med Genet. 2020 Aug 11;7(1):10. doi: 10.1186/s40575-020-00089-5.

ABSTRACT

BACKGROUND: Evidence for an autoimmune etiology in canine diabetes is inconsistent and could vary based on breed. Previous studies demonstrated that small percentages of diabetic dogs possess autoantibodies to antigens known to be important in human type 1 diabetes, but most efforts involved analysis of a wide variety of breeds. The objective of this study was to evaluate the presence of glutamic acid decarboxylase 65 (GAD65), insulinoma-associated protein 2 (IA-2), and zinc transporter 8 (ZnT8) autoantibodies in diabetic and non-diabetic Australian Terriers and Samoyeds, two breeds with comparatively high prevalence of diabetes, in the United States.

RESULTS: There was no significant difference in the proportion of samples considered positive for GAD65 or ZnT8 autoantibodies in either breed evaluated, or for IA-2 autoantibodies in Australian Terriers (p > 0.05). The proportion of IA-2 autoantibody positive samples was significantly higher in diabetic versus non-diabetic Samoyeds (p = 0.003), but substantial overlap was present between diabetic and non-diabetic groups.

CONCLUSIONS: The present study does not support GAD65, IA-2, or ZnT8 autoantibodies as markers of autoimmunity in canine diabetes in Samoyeds or Australian Terriers as measured using human antigen sandwich enzyme-linked immunosorbent (ELISA) assays. Future studies using canine specific assays as well as investigation for alternative markers of autoimmunity in these and other canine breeds are warranted.

PMID:33323126 | PMC:PMC7491469 | DOI:10.1186/s40575-020-00089-5

Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion

Fetched: February 24th, 2021, 5:01am GMT by Guo-Fang Zhang

Cell Metab. 2020 Dec 8:S1550-4131(20)30655-0. doi: 10.1016/j.cmet.2020.11.020. Online ahead of print.

ABSTRACT

Metabolic fuels regulate insulin secretion by generating second messengers that drive insulin granule exocytosis, but the biochemical pathways involved are incompletely understood. Here we demonstrate that stimulation of rat insulinoma cells or primary rat islets with glucose or glutamine + 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (Gln + BCH) induces reductive, "counter-clockwise" tricarboxylic acid (TCA) cycle flux of glutamine to citrate. Molecular or pharmacologic suppression of isocitrate dehydrogenase-2 (IDH2), which catalyzes reductive carboxylation of 2-ketoglutarate to isocitrate, results in impairment of glucose- and Gln + BCH-stimulated reductive TCA cycle flux, lowering of NADPH levels, and inhibition of insulin secretion. Pharmacologic suppression of IDH2 also inhibits insulin secretion in living mice. Reductive TCA cycle flux has been proposed as a mechanism for generation of biomass in cancer cells. Here we demonstrate that reductive TCA cycle flux also produces stimulus-secretion coupling factors that regulate insulin secretion, including in non-dividing cells.

PMID:33321098 | DOI:10.1016/j.cmet.2020.11.020

Pasireotide: A Novel Treatment for Tumor-Induced Hypoglycemia Due to Insulinoma and Non-Islet Cell Tumor Hypoglycemia

Fetched: February 24th, 2021, 5:01am GMT by Mahwash Siddiqui

J Endocr Soc. 2020 Nov 5;5(1):bvaa171. doi: 10.1210/jendso/bvaa171. eCollection 2021 Jan 1.

ABSTRACT

Tumor-induced hypoglycemia is a serious disorder most commonly caused by insulinoma or non-islet cell tumor hypoglycemia (NICTH). The hypoglycemia can be severe and refractory to conventional therapy, leading to significant morbidity and mortality. The objective of this work is to describe a series of challenging cases in which refractory, tumor-induced hypoglycemia was shown to respond to the use of pasireotide, a second-generation somatostatin receptor ligand. We describe the clinical and biochemical features of 3 patients with tumor-induced hypoglycemia due to an occult insulinoma, malignant insulinoma, and non-islet cell tumor hypoglycemia. In these 3 individuals, the hypoglycemia remained refractory to guideline-recommended medical therapy, such as diazoxide, nonpasireotide somatostatin analogues, and glucocorticoids. Pasireotide was substituted to attenuate the refractory hypoglycemia for each patient. The addition of pasireotide led to prompt improvement in the frequency and severity of hypoglycemic episodes for each tumor-induced hypoglycemia patient. We demonstrate the successful treatment of 3 individuals with refractory, tumor-induced hypoglycemia with pasireotide. We offer the first reported use of pasireotide for the successful treatment of nonmalignant insulinoma and non-islet cell tumor hypoglycemia.

PMID:33294765 | PMC:PMC7692539 | DOI:10.1210/jendso/bvaa171

Insulinoma in pregnancy (a case presentation and systematic review of the literature)

Fetched: February 24th, 2021, 5:01am GMT by Eva M Dobrindt

Rare Tumors. 2021 Feb 7;13:2036361320986647. doi: 10.1177/2036361320986647. eCollection 2021.

ABSTRACT

Insulinomas are rare, benign and functional tumors that coincidentally may become overt during pregnancy or in the post-partum period. As the general symptoms of a pregnancy might cover the clinical presentation, diagnosing remains challenging. We present one additional case of a post-partum insulinoma, combined with a systematic review of the literature to sum up relevant details in diagnosis and treatment. A systematic request of Pubmed/Medline was conducted using the following terms: "insulinoma AND pregnancy" and "insulinoma" for a second request of ClinicalTrials.gov. All publications concerning pregnant or post-partum women with insulinoma were included. Thirty-six cases could be identified for analysis. Each publication was reviewed for demographic, diagnostic and therapeutic data. The most frequent clinical signs were unconsciousness and neurological symptoms. 64.9% were diagnosed during early pregnancy and 35.1% post-partum. 91.9% underwent surgery with a third resected during pregnancy without severe influence on fetal or maternal outcome. Three patients died of metastatic disease or misdiagnosing, two of them miscarried. Insulinoma in pregnancy is rare but should be considered in case of unclear hyperinsulinemic hypoglycemia. Surgery can be performed during the second trimester or post-partum with promising outcome.

PMID:33613925 | PMC:PMC7874339 | DOI:10.1177/2036361320986647

Permalink for 'Neuroendocrine differentiation in a large series of genetically-confirmed Ewing's sarcoma family tumor: Does it provide any diagnostic or prognostic information?'

Neuroendocrine differentiation in a large series of genetically-confirmed Ewing's sarcoma family tumor: Does it provide any diagnostic or prognostic information?

Fetched: February 24th, 2021, 5:01am GMT by Isidro Machado

Pathol Res Pract. 2021 Mar;219:153362. doi: 10.1016/j.prp.2021.153362. Epub 2021 Feb 6.

ABSTRACT

Given the potential for neuroendocrine differentiation in Ewing's sarcoma family of tumors (ESFT), we aimed to determine neuroendocrine expression in a large series of genetically-confirmed ESFT and its prognostic significance in clinically-localised neoplasms (n = 176). Slides prepared from tissue microarrays were stained for Insulinoma-associated protein 1 (INSM1), CD56, chromogranin-A and synaptophysin. INSM1 expression was present in 59% of ESFT, while synaptophysin, chromogranin-A and CD56 were expressed in only 13%, 8% and 5% of ESFT, respectively. Histological subtypes were only significantly correlated with INSM1 (p = 0.032) or CD56 (p = 0.016) immunoexpression. Regarding prognosis, no significant association was found between INSM1, synaptophysin or chromogranin-A immunoexpression and progression-free survival (PFS) or overall survival (OS). Despite the low proportion of tumors with CD56 immunoreactivity, CD56 expression was shown to correlate with both poor PFS (p < 0.001) and poor OS (p < 0.001) in the present series. In conclusion, neuroendocrine differentiation is often present in ESFT, and in the present study INSM1 expression in particular was found to be higher than previously described in Ewing's tumors. Nevertheless, this finding does not distinguish these tumors from other round cell tumors that may show focal or diffuse neuroendocrine differentiation. CD56 expression could be used as a prognostic factor in ESFT, although given the results herein obtained, we recommend a prospective validation in independent series including localized and disseminated tumors in ESFT.

PMID:33610950 | DOI:10.1016/j.prp.2021.153362

CD81 marks immature and dedifferentiated pancreatic β-cells

Fetched: February 24th, 2021, 5:01am GMT by Ciro Salinno

Mol Metab. 2021 Feb 11;49:101188. doi: 10.1016/j.molmet.2021.101188. Online ahead of print.

ABSTRACT

OBJECTIVE: Islets of Langerhans contain heterogeneous populations of insulin-producing β-cells. Surface markers and respective antibodies for isolation, tracking, and analysis are urgently needed to study β-cell heterogeneity and explore the mechanisms to harness the regenerative potential of immature β-cells.

METHODS: We performed single-cell mRNA profiling of early postnatal mouse islets and re-analyzed several single-cell mRNA sequencing datasets from mouse and human pancreas and islets. We used mouse primary islets, iPSC-derived endocrine cells, Min6 insulinoma, and human EndoC-βH1 β-cell lines and performed FAC sorting, Western blotting, and imaging to support and complement the findings from the data analyses.

RESULTS: We found that all endocrine cell types expressed the cluster of differentiation 81 (CD81) during pancreas development, but the expression levels of this protein were gradually reduced in β-cells during postnatal maturation. Single-cell gene expression profiling and high-resolution imaging revealed an immature signature of β-cells expressing high levels of CD81 (CD81^high) compared to a more mature population expressing no or low levels of this protein (CD81^low/-). Analysis of β-cells from different diabetic mouse models and in vitro β-cell stress assays indicated an upregulation of CD81 expression levels in stressed and dedifferentiated β-cells. Similarly, CD81 was upregulated and marked stressed human β-cells in vitro.

CONCLUSIONS: We identified CD81 as a novel surface marker that labels immature, stressed, and dedifferentiated β-cells in the adult mouse and human islets. This novel surface marker will allow us to better study β-cell heterogeneity in healthy subjects and diabetes progression.

PMID:33582383 | PMC:PMC7932895 | DOI:10.1016/j.molmet.2021.101188

Imaging of Insulinoma by Targeting Glucagonlike Peptide-1 Receptor.

Fetched: February 18th, 2021, 5:01am GMT

PET Clin. 2021 Apr;16(2):205-217. doi: 10.1016/j.cpet.2020.12.008. Epub 2021 Feb 12.

ABSTRACT

"Glucagonlike peptide-1 (GLP-1) receptor imaging, using radiolabeled exendin-4, was recently established for detecting insulinoma in patients with hyperinsulinemic hypoglycemia. It has proven to be a sensitive and specific method for preoperative localization of insulinoma. This review introduces the development, clinical research, and perspective of GLP-1 receptor imaging mainly in insulinoma.

PMID:33589387 | DOI:10.1016/j.cpet.2020.12.008

In vitro Characterization of Insulin-Producing β-Cell Spheroids.

Fetched: February 17th, 2021, 5:01am GMT

Front Cell Dev Biol. 2021 Jan 28;8:623889. doi: 10.3389/fcell.2020.623889. eCollection 2020.

ABSTRACT

Over the years, immortalized rodent β-cell lines such as RIN, HIT, MIN, βTC, and INS-1 have been used to investigate pancreatic β-cell physiology using conventional two-dimensional (2D) culture techniques. However, physical and physiological limitations inherent to 2D cell culture necessitates confirmatory follow up studies using sentient animals. Three-dimensional (3D) culture models are gaining popularity for their recapitulation of key features of in vivo organ physiology, and thus could pose as potential surrogates for animal experiments. In this study, we aimed to develop and characterize a rat insulinoma INS-1 3D spheroid model to compare with 2D monolayers of the same cell line. Ultrastructural verification was done by transmission electron microscopy and toluidine blue staining, which showed that both 2D monolayers and 3D spheroids contained highly granulated cells with ultrastructural features synonymous with mature pancreatic β-cells, with increased prominence of these features observed in 3D spheroids. Viability, as assessed by cellular ATP quantification, size profiling and glucose utilization, showed that our spheroids remained viable for the experimental period of 30 days, compared to the limiting 5-day passage period of INS-1 monolayers. In fact, increasing ATP content together with spheroid size was observed over time, without adverse changes in glucose utilization. Additionally, β-cell function, assessed by determining insulin and amylin secretion, showed that the 3D spheroids retained glucose sensing and insulin secretory capability, that was more acute when compared to 2D monolayer cultures. Thus, we were able to successfully demonstrate that our in vitro INS-1 β-cell 3D spheroid model exhibits in vivo tissue-like structural features with extended viability and lifespan. This offers enhanced predictive capacity of the model in the study of metabolic disease, β-cell pathophysiology and the potential treatment thereof.

PMID:33585464 | PMC:PMC7876261 | DOI:10.3389/fcell.2020.623889

Nanomolar melatonin influences insulin synthesis and secretion in rat insulinoma INS-1E cells.

Fetched: February 13th, 2021, 5:01am GMT

J Physiol Pharmacol. 2020 Oct;71(5). doi: 10.26402/jpp.2020.5.10. Epub 2021 Feb 8.

ABSTRACT

Pancreatic beta-cell dysfunction results in reductions of insulin synthesis/secretion, cell survival, and insulin sensitivity thereby inducing diabetes mellitus. In this study, how nanomolar melatonin regulates insulin synthesis and secretion in rat insulinoma INS-1E cells was investigated. At melatonin concentrations of 10 - 100 nM for 48 hours, melatonin significantly increased the insulin protein level in INS-1E cells above the level in control cells without melatonin or glucose treatments and decreased the insulin level in media with glucose: increases in insulin synthesis and decreases in insulin secretion occurred in dose-dependent manners. Luzindole or 4-phenyl-2-propionamidotetralin (4P-PDOT), melatonin receptor antagonists, inhibited the melatonin-induced insulin level in cells and media. Levels of membrane vesicle trafficking-related proteins including Rab5, GOPC, phospho-caveolin-1, EEA1, and clathrin proteins significantly increased with melatonin treatment above that in control cells without melatonin or glucose treatments, whereas expressions of APPL1 and syntaxin-6 proteins significantly decreased with melatonin treatment. The increases in the phosphorylation of mammalian target of rapamycin (p-mTOR), raptor protein, and mTOR complex 1 (mTORC1) levels were consistent with the increments in the expressions of p-Akt (Ser473, Thr308) and stress-induced IRE1α/p-eIF2α proteins in the endoplasmic reticulum following melatonin treatment. also, expression levels of Bcl-2 and Bcl-xl proteins were significantly increased compared to those in control cells without melatonin or glucose treatments, whereas the Bax protein level decreased. These results indicate that nanomolar melatonin regulates insulin synthesis and secretion associated with membrane vesicle trafficking-related proteins, including Rab5, GOPC, p-Caveolin-1, EEA1, and clathrin, through the Akt/mTOR pathway.

PMID:33571963 | DOI:10.26402/jpp.2020.5.10

Endothelial Cell-Derived Triosephosphate Isomerase Attenuates Insulin Secretion From Pancreatic Beta Cells of Male Rats.

Fetched: February 13th, 2021, 5:01am GMT

Endocrinology. 2021 Mar 1;162(3):bqaa234. doi: 10.1210/endocr/bqaa234.

ABSTRACT

Insulin secretion from pancreatic beta cells is tightly regulated by glucose and paracrine signals within the microenvironment of islets of Langerhans. Extracellular matrix from islet microcapillary endothelial cells (IMEC) affect beta-cell spreading and amplify insulin secretion. This study was aimed at investigating the hypothesis that contact-independent paracrine signals generated from IMEC may also modulate beta-cell insulin secretory functions. For this purpose, conditioned medium (CMp) preparations were prepared from primary cultures of rat IMEC and were used to simulate contact-independent beta cell-endothelial cell communication. Glucose-stimulated insulin secretion (GSIS) assays were then performed on freshly isolated rat islets and the INS-1E insulinoma cell line, followed by fractionation of the CMp, mass spectroscopic identification of the factor, and characterization of the mechanism of action. The IMEC-derived CMp markedly attenuated first- and second-phase GSIS in a time- and dose-dependent manner without altering cellular insulin content and cell viability. Size exclusion fractionation, chromatographic and mass-spectroscopic analyses of the CMp identified the attenuating factor as the enzyme triosephosphate isomerase (TPI). An antibody against TPI abrogated the attenuating activity of the CMp while recombinant human TPI (hTPI) attenuated GSIS from beta cells. This effect was reversed in the presence of tolbutamide in the GSIS assay. In silico docking simulation identified regions on the TPI dimer that were important for potential interactions with the extracellular epitopes of the sulfonylurea receptor in the complex. This study supports the hypothesis that an effective paracrine interaction exists between IMEC and beta cells and modulates glucose-induced insulin secretion via TPI-sulfonylurea receptor-KATP channel (SUR1-Kir6.2) complex attenuating interactions.

PMID:33570112 | DOI:10.1210/endocr/bqaa234

Saturated fatty acids entrap PDX1 in stress granules and impede islet beta cell function.

Fetched: February 13th, 2021, 5:01am GMT

Diabetologia. 2021 May;64(5):1144-1157. doi: 10.1007/s00125-021-05389-4. Epub 2021 Feb 11.

ABSTRACT

AIMS/HYPOTHESIS: Failure of pancreatic and duodenal homeobox factor 1 (PDX1) to localise in the nucleus of islet beta cells under high-fat diet (HFD) conditions may be an early functional defect that contributes to beta cell failure in type 2 diabetes; however, the mechanism of PDX1 intracellular mislocalisation is unclear. Stress granules (SGs) are membrane-less cytoplasmic structures formed under stress that impair nucleocytoplasmic transport by sequestering nucleocytoplasmic transport factors and components of the nuclear pore complex. In this study, we investigated the stimulators that trigger SG formation in islet beta cells and the effects of SGs on PDX1 localisation and beta cell function.

METHODS: The effect of palmitic acid (PA) on nucleocytoplasmic transport was investigated by using two reporters, S-tdTomato and S-GFP. SG assembly in rat insulinoma cell line INS1 cells, human islets under PA stress, and the pancreas of diet-induced obese mice was analysed using immunofluorescence and immunoblotting. SG protein components were identified through mass spectrometry. SG formation was blocked by specific inhibitors or genetic deletion of essential SG proteins, and then PDX1 localisation and beta cell function were investigated in vitro and in vivo.

RESULTS: We showed that saturated fatty acids (SFAs) are endogenous stressors that disrupted nucleocytoplasmic transport and stimulated SG formation in pancreatic beta cells. Using mass spectrometry approaches, we revealed that several nucleocytoplasmic transport factors and PDX1 were localised to SGs after SFA treatment, which inhibited glucose-induced insulin secretion. Furthermore, we found that SFAs induced SG formation in a phosphoinositide 3-kinase (PI3K)/eukaryotic translation initiation factor 2α (EIF2α) dependent manner. Disruption of SG assembly by PI3K/EIF2α inhibitors or genetic deletion of T cell restricted intracellular antigen 1 (TIA1) in pancreatic beta cells effectively suppressed PA-induced PDX1 mislocalisation and ameliorated HFD-mediated beta cell dysfunction.

CONCLUSIONS/INTERPRETATION: Our findings suggest a link between SG formation and beta cell dysfunction in the presence of SFAs. Preventing SG formation may be a potential therapeutic strategy for treating obesity and type 2 diabetes.

PMID:33569632 | DOI:10.1007/s00125-021-05389-4

MAXIMIZING THE UTILITY OF THE 72-HOUR FAST IN EVALUATING HYPOGLYCEMIA.

Fetched: February 13th, 2021, 5:01am GMT

Endocr Pract. 2021 Jan;27(1):80-81. doi: 10.1016/j.eprac.2020.11.005. Epub 2020 Nov 17.

NO ABSTRACT

PMID:33475507 | DOI:10.1016/j.eprac.2020.11.005

Permalink for 'Morus alba leaves ethanol extract protects pancreatic islet cells against dysfunction and death by inducing autophagy in type 2 diabetes.'

Morus alba leaves ethanol extract protects pancreatic islet cells against dysfunction and death by inducing autophagy in type 2 diabetes.

Fetched: February 12th, 2021, 5:01am GMT

Phytomedicine. 2021 Mar;83:153478. doi: 10.1016/j.phymed.2021.153478. Epub 2021 Jan 28.

ABSTRACT

BACKGROUND: Protection of pancreatic islet cells against dysfunction or death by regulating autophagy is considered to be an effective method for treatment of type 2 diabetes mellitus (T2DM). Morus alba leaves (mulberry leaves), a popular herbal medicine, have been used for prevention of T2DM since ancient times.

PURPOSE: This study aimed to clarify whether Morus alba leaves ethanol extract (MLE) could protect islet cells in vivo and in vitro by regulating autophagy in T2DM, and explore the possible mechanism of action.

METHODS: The main chemical constituents in MLE were analyzed by HPLC. The T2DM rat model was induced via high-fat diet combined with peritoneal injection of low-dose streptozotocin, and MLE was administered by oral gavage. Fasting blood glucose (FBG) and plasma insulin were measured, and homeostatic model assessment of β cell function (HOMA-β) and insulin resistance (HOMA-IR) were determined. The histomorphology of pancreas islets was evaluated by haematoxylin and eosin staining. In palmitic acid (PA)-stressed INS-1 rat insulinoma cells, cell viability was assayed by an MTT method. Expression of the autophagy-related proteins LC3 I/II, p62, p-AMPK and p-mTOR in islet tissues and INS-1 cells was evaluated by western blotting or immunohistochemistry analysis.

RESULTS: The four main chemical constituents in MLE were identified as chlorogenic acid, rutin, isoquercitrin and quercitrin. MLE ameliorated hyperglycemia, insulin resistance and dyslipidemia of T2DM rats with prominent therapeutic effect. Further study indicated that MLE observably improved islet function, alleviated islet injury of T2DM rats, and inhibited PA-induced INS-1 cell death. On the other hand, MLE significantly induced autophagy in islet cells both in vivo and in vitro, and autophagy inhibitors abolished its therapeutic effect on T2DM rats and protective effect on islet cells. Apart from this, MLE markedly activated the AMPK/mTOR pathway in INS-1 cells, and the AMPK inhibitor prevented the autophagy induction ability of MLE.

CONCLUSION: Together, MLE could protect islet cells against dysfunction and death by inducing AMPK/mTOR-mediated autophagy in T2DM, and these findings provide a new perspective for understanding the treatment mechanism of Morus alba leaves against T2DM.

PMID:33567371 | DOI:10.1016/j.phymed.2021.153478

Clinical Impact of Organ-Preserving Surgery for Pancreatic Neuroendocrine Neoplasms: A Single-Center Experience.

Fetched: February 12th, 2021, 5:01am GMT

Pancreas. 2021 Feb 1;50(2):196-200. doi: 10.1097/MPA.0000000000001739.

ABSTRACT

OBJECTIVES: Organ-preserving surgery (OPS) has been accepted for pancreatic neuroendocrine neoplasms, particularly for the management of small tumors. This study aimed to analyze the surgical outcome following this treatment at our institute, focusing on the perioperative factors and postoperative locoregional recurrence.

METHODS: We analyzed 71 consecutive patients with no synchronous liver metastasis. These patients were classified into 1 of 2 groups: the standard operation group (SOG, 41 patients) with prophylactic regional lymph node dissection and the organ-preserving surgery group (OPG, 30 patients). We performed OPS based on size criteria (tumor size <1.5 cm in nonfunctional pancreatic neuroendocrine neoplasms and <2 cm in insulinoma with no evident bulky lymph node swelling on preoperative imaging).

RESULTS: The median follow-up periods were 37 months. The OPG included enucleation, partial resection, proximal parenchymal pancreatectomy, central pancreatectomy, spleen-preserving distal pancreatectomy, and Warshaw operation. The SOG included pancreatoduodenectomy and distal pancreatectomy, showing no statistically significant differences between the 2 groups in terms of operation time, hospitalization duration, and postoperative complications. Ten patients showed lymph node metastasis (25%) only in the SOG. There were no locoregional recurrent cases in the OPG.

CONCLUSIONS: In selected patients, OPS may be effective based on the appropriate tumor size criteria.

PMID:33565795 | DOI:10.1097/MPA.0000000000001739

Continuous Glucose Monitoring in Patients With Insulinoma Treated by Endoscopic Ultrasound-Guided Ethanol Injection.

Fetched: February 11th, 2021, 5:01am GMT

Pancreas. 2021 Feb 1;50(2):183-188. doi: 10.1097/MPA.0000000000001735.

ABSTRACT

OBJECTIVES: The aims of this study were to analyze the continuous glucose monitoring (CGM) profiles of patients with insulinoma before and after treatment with endoscopic ultrasound-guided ethanol injection and assess the value of CGM in curative effect evaluating.

METHODS: We included 8 patients, and CGM was performed for 3 to 5 days before and after treatment.

RESULTS: The proportion of monitoring points at which the glucose level was lower than 3.9 mmol/L after treatment decreased in patient 5 (from 4% to 3%) and patient 8 (from 30% to 12%), whereas the proportion increased in patient 1 (from 1% to 16%), patient 3 (from 5% to 23%), and patient 7 (from 7% to 63%). There was no mean significant difference between CGM values (5.75 [standard deviation, 2.49] mmol/L) and self-monitoring of blood glucose values (5.76 [standard deviation, 2.32] mmol/L) (P > 0.05). Pearson correlation analysis showed positive correlation between CGM values and self-monitoring of blood glucose values (r = 0.88, P < 0.05). Clarke Error Grid Analysis showed that 91.5% of pairs were located in areas A and B.

CONCLUSIONS: Continuous glucose monitoring is useful for detecting hypoglycemia and evaluating curative effect, but the correction of fingertip blood glucose is necessary when the blood glucose is relatively low.

PMID:33560091 | DOI:10.1097/MPA.0000000000001735

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