Condition: Insulinoma
Interventions: Drug: [68Ga]Ga-HBED-CC-exendin-4; Drug: [68Ga]Ga-NOTA-exendin-4
Sponsor: Peking Union Medical College Hospital
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Trial - Insulinoma
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![Permalink for '[68Ga]Ga-HBED-CC-exendin-4 and [68Ga]Ga-NOTA-exendin-4 PET/CT Imaging in the Same Group of Insulinoma Patients'](/themes/orange-slice/web/media/pl.gif)
[68Ga]Ga-HBED-CC-exendin-4 and [68Ga]Ga-NOTA-exendin-4 PET/CT Imaging in the Same Group of Insulinoma Patients
Posted: September 3rd, 2021, 2:00pm GMT
Google - Insulinoma
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The Item Parents of Children with Diabetes Need on Their Back-to-School List - SheKnows
Posted: September 15th, 2021, 5:33pm GMT
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Insulinoma: Overview and More - Verywell Health
Posted: September 13th, 2021, 11:58am GMT
Insulinoma: Overview and More Verywell Health -
Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs - pnas.org
Posted: September 10th, 2021, 6:13pm GMT
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Pancreatic Endocrine Tumor Market Insights and Treatment Mar... - MENAFN.COM
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Pancreatic Endocrine Tumor Market Insights and Treatment Market by DelveInsight - Digital Journal
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Insulinoma Market Competition by Manufacturer,Mergers & Acquisitions Planning,Top 5 Manufacturer Market Share – SoccerNurds - SoccerNurds
Posted: September 9th, 2021, 10:50am GMT
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Cathepsin H high expression in thyroid carcinoma | IJGM - Dove Medical Press
Posted: September 6th, 2021, 12:24pm GMT
Cathepsin H high expression in thyroid carcinoma | IJGM Dove Medical Press -
Baqsimi: Side effects and how to manage them - Medical News Today
Posted: August 25th, 2021, 5:00am GMT
Baqsimi: Side effects and how to manage them Medical News Today -
Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer - DocWire News
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Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer - DocWire News
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More and More U.S. Kids Being Diagnosed With Diabetes - MedPage Today
Posted: August 24th, 2021, 1:00pm GMT
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Xeris Pharmaceuticals Announces Approval of Supplemental New Drug Application (sNDA) of Gvoke® Kit for the Treatment of Severe Hypoglycemia - BioSpace
Posted: August 23rd, 2021, 10:00am GMT
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Did You Know There Are 4 Types Of PCOS? Find Out Their Causes And Treatments - NDTV
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Insulinoma Market Size, Top Key Players, Types, Applications & Forecasts 2021 – 2027 – Murphy's Hockey Law - Murphy's Hockey Law
Posted: August 17th, 2021, 4:16am GMT
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Xeris Pharmaceuticals Achieves Unprecedented Levels of Payor Coverage for Gvoke® - Business Wire
Posted: August 13th, 2021, 10:00am GMT
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Global Insulinoma Market 2021 Outlook and Study of Top Players – Abcam, Ciron Group, Pfizer, Entax Medical, Olympus - The Manomet Current
Posted: August 11th, 2021, 6:55am GMT
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Type 2 Diabetes pathogenesis and treatments | DMSO - Dove Medical Press
Posted: August 9th, 2021, 8:24pm GMT
Type 2 Diabetes pathogenesis and treatments | DMSO Dove Medical Press -
Efficacy, Pharmacokinetics, Biodistribution and Excretion of a Novel A | DDDT - Dove Medical Press
Posted: August 9th, 2021, 7:10pm GMT
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Insulinoma Market by Technology Advancement and Demand 2021-2026 - Market Primes
Posted: August 5th, 2021, 12:47pm GMT
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Eiger Announces FDA Breakthrough Therapy Designation for Avexitide for Treatment of Congenital Hyperinsulinism - Yahoo Finance
Posted: August 5th, 2021, 10:00am GMT
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Eiger Announces FDA Breakthrough Therapy Designation for Avexitide for Treatment of Congenital Hyperinsulinism - PRNewswire
Posted: August 5th, 2021, 5:00am GMT
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APAC, Europe, America region to materialize major revenue contributor for Global Insulinoma market through 2026 - Market Primes
Posted: August 3rd, 2021, 5:37am GMT
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Xeris Pharmaceuticals Enters Into an Exclusive License and Supply Agreement with Tetris Pharma Limited to Commercialize Ogluo® in Europe - BioSpace
Posted: July 19th, 2021, 5:00am GMT
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Walmart Is Offering a More Affordable Brand of Insulin - Verywell Health
Posted: July 1st, 2021, 5:00am GMT
Walmart Is Offering a More Affordable Brand of Insulin Verywell Health -
Zegalogue Now Available for Severe Hypoglycemia - Monthly Prescribing Reference
Posted: June 24th, 2021, 5:00am GMT
Zegalogue Now Available for Severe Hypoglycemia Monthly Prescribing Reference -
Novel enzymatic cross-linking–based hydrogel nanofilm caging system on pancreatic β cell spheroid for long-term blood glucose regulation - Science Advances
Posted: June 23rd, 2021, 5:00am GMT
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Novel enzymatic cross-linking–based hydrogel nanofilm caging system on pancreatic β cell spheroid for long-term blood glucose regulation - Science Advances
Posted: June 23rd, 2021, 5:00am GMT
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Zealand Pharma to Present Data on Glucagon Analog, Dasiglucagon, at the 81st Annual American Diabetes Association Scientific Sessions - Yahoo Finance
Posted: June 16th, 2021, 5:00am GMT
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Potential Blood Sugar Test Uses Sweat, Not Blood - WebMD
Posted: June 2nd, 2021, 5:00am GMT
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Benign Tumor: Overview and More - Verywell Health
Posted: May 14th, 2021, 5:00am GMT
Benign Tumor: Overview and More Verywell Health -
Can I Get a Headache After Eating Sugar or Fasting from Sugar? - Verywell Health
Posted: May 7th, 2021, 5:00am GMT
Can I Get a Headache After Eating Sugar or Fasting from Sugar? Verywell Health -
Zealand Pharma announces publication of Phase 3 trial evaluating efficacy and safety of dasiglucagon for treatment - GlobeNewswire
Posted: May 3rd, 2021, 5:00am GMT
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Xeris Pharmaceuticals Receives U.K. MHRA Approval of Ogluo® (glucagon) Injection for the Treatment of Severe Hypoglycaemia in Adults, Adolescents, and Children Aged 2 Years and Over With Diabetes Mellitus - Yahoo Finance
Posted: April 29th, 2021, 5:00am GMT
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Anti-aging compound improves muscle glucose metabolism in people: Further studies underway to determine extent of clinical benefits - Science Daily
Posted: April 22nd, 2021, 5:00am GMT
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Detection of feline insulinoma with contrast-enhanced ultrasonography - DVM 360
Posted: April 11th, 2021, 5:00am GMT
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What You Should Know About the IPMN Tumor - Verywell Health
Posted: March 25th, 2021, 5:00am GMT
What You Should Know About the IPMN Tumor Verywell Health -
Zealand Pharma Announces FDA Approval of Zegalogue® (dasiglucagon) injection, for the Treatment of Severe Hypoglycemia in People with Diabetes - Yahoo Finance
Posted: March 22nd, 2021, 5:00am GMT
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A Mixed Meal Tolerance Test for Clinical Trials - Verywell Health
Posted: March 3rd, 2021, 6:00am GMT
A Mixed Meal Tolerance Test for Clinical Trials Verywell Health -
Sweet dreams: Use of low-dose dexmedetomidine for perioperative management of canine insulinoma - DVM 360
Posted: March 3rd, 2021, 6:00am GMT
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Cancer Death Rates Continue to Fall in Europe, Except For... - Medscape
Posted: February 23rd, 2021, 6:00am GMT
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Adrenal Cancer: Overview and More - Verywell Health
Posted: February 20th, 2021, 6:00am GMT
Adrenal Cancer: Overview and More Verywell Health -
Prediabetes May Harm Your Brain - WebMD
Posted: February 17th, 2021, 6:00am GMT
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Brain Cancer Overview and More - Verywell Health
Posted: February 9th, 2021, 6:00am GMT
Brain Cancer Overview and More Verywell Health -
Non autoimmune type 1B diabetes after mild COVID‐19: Report of three cases - Wiley
Posted: February 3rd, 2021, 6:00am GMT
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What Is a Tumor? - Verywell Health
Posted: January 24th, 2021, 6:00am GMT
What Is a Tumor? Verywell Health -
Exotic animals may be good option for some - The Concord Insider
Posted: December 9th, 2020, 6:00am GMT
Exotic animals may be good option for some The Concord Insider -
New listings in AVMA Animal Health Studies Database - American Veterinary Medical Association
Posted: November 15th, 2020, 6:00am GMT
New listings in AVMA Animal Health Studies Database American Veterinary Medical Association -
Receptor-Targeted Photodynamic Therapy of Glucagon-Like Peptide 1 Receptor–Positive Lesions - Journal of Nuclear Medicine
Posted: November 1st, 2020, 5:00am GMT
Receptor-Targeted Photodynamic Therapy of Glucagon-Like Peptide 1 Receptor–Positive Lesions Journal of Nuclear Medicine -
Children with multiple islet autoantibodies are more likely to progress to type 1 diabetes - News-Medical.Net
Posted: October 30th, 2020, 5:00am GMT
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How a Virus Can Trigger Diabetes - Genetic Engineering & Biotechnology News
Posted: October 26th, 2020, 5:00am GMT
How a Virus Can Trigger Diabetes Genetic Engineering & Biotechnology News -
What Are Neuroendocrine Tumors (NETs)? - Cancer - Verywell Health
Posted: October 22nd, 2020, 5:00am GMT
What Are Neuroendocrine Tumors (NETs)? - Cancer Verywell Health -
How to recognise the symptoms of hypoglycemia, or low blood sugar - Business Insider Australia
Posted: September 16th, 2020, 5:00am GMT
How to recognise the symptoms of hypoglycemia, or low blood sugar Business Insider Australia -
Insulinoma and Excess Insulin: Symptoms, Causes, Diagnosis, Treatment - WebMD
Posted: July 27th, 2020, 5:00am GMT
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COVID-19 Risks When You Have Diabetes - WebMD
Posted: July 22nd, 2020, 5:00am GMT
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Diabetic Shock and Insulin Reactions: Causes, Symptoms, and Treatments - WebMD
Posted: July 17th, 2020, 5:00am GMT
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She Was Healthy and Active. Suddenly She Had a Seizure. - The New York Times
Posted: July 1st, 2020, 5:00am GMT
She Was Healthy and Active. Suddenly She Had a Seizure. The New York Times -
Xeris Pharmaceuticals Announces Gvoke HypoPen™ – the First Autoinjector for Severe Hypoglycemia – Now Available - Business Wire
Posted: July 1st, 2020, 5:00am GMT
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Proglycem: Dosage, side effects, uses, and more - Medical News Today
Posted: June 27th, 2020, 5:00am GMT
Proglycem: Dosage, side effects, uses, and more Medical News Today -
Gvoke: Dosage, how to use, alternatives, and more - Medical News Today
Posted: June 4th, 2020, 5:00am GMT
Gvoke: Dosage, how to use, alternatives, and more Medical News Today -
New Holstein golfer Shaelynn Feuerstein was ready to make history after battling rare tumor - The Sheboygan Press
Posted: May 5th, 2020, 5:00am GMT
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Clinical Challenges: Nuclear Medicine and Neuroendocrine Tumors - MedPage Today
Posted: April 30th, 2020, 5:00am GMT
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Treatment Options for Pancreatic Neuroendocrine Tumors - Endocrinology Advisor
Posted: March 2nd, 2020, 6:00am GMT
Treatment Options for Pancreatic Neuroendocrine Tumors Endocrinology Advisor -
Pancreatic cancer: Symptoms, causes, and treatment - Medical News Today
Posted: February 13th, 2020, 7:51pm GMT
Pancreatic cancer: Symptoms, causes, and treatment Medical News Today -
Fresenius Kabi Introduces Glucagon Emergency Medicine Kit to Treat Life-Threatening Episodes of Low Blood Sugar - Business Wire
Posted: February 5th, 2020, 6:00am GMT
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Pancreatic cancer treatment: Why do you need a second opinion? - Times Now
Posted: November 18th, 2019, 6:00am GMT
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Hyperinsulinemia: Causes, treatments, and related conditions - Medical News Today
Posted: September 17th, 2019, 5:00am GMT
Hyperinsulinemia: Causes, treatments, and related conditions Medical News Today -
GVOKE Injection Gains FDA Approval - PrecisionVaccinations
Posted: September 13th, 2019, 5:00am GMT
GVOKE Injection Gains FDA Approval PrecisionVaccinations -
FDA OKs Easy-to-Use Glucagon Rescue Pen for Hypos in Diabetes - Medscape
Posted: September 11th, 2019, 5:00am GMT
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Xeris Pharmaceuticals Receives U.S. FDA Approval for GVOKE™ (glucagon), the First Ready-to-use Stable Liquid Glucagon for Severe Hypoglycemia - Business Wire
Posted: September 10th, 2019, 5:00am GMT
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Aretha Franklin's Detroit-based doctor talks about the cancer that took her life - Detroit Free Press
Posted: August 16th, 2019, 5:00am GMT
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Eli Lilly's BAQSIMI nasal powder set to treat severe hypoglycemia - BSA bureau
Posted: July 25th, 2019, 5:00am GMT
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1st Severe Hypoglycemia Treatment Administered Without an Injection Gains FDA Approval - PrecisionVaccinations
Posted: July 25th, 2019, 5:00am GMT
1st Severe Hypoglycemia Treatment Administered Without an Injection Gains FDA Approval PrecisionVaccinations -
Types of diabetes tests - Medical News Today
Posted: July 12th, 2019, 5:00am GMT
Types of diabetes tests Medical News Today -
Kaplan USMLE Step 1 prep: Woman has excessive thirst, urination - American Medical Association
Posted: May 14th, 2019, 5:00am GMT
Kaplan USMLE Step 1 prep: Woman has excessive thirst, urination American Medical Association -
Insulinoma resembling a rapid eye movement sleep behavior disorder: a | IMCRJ - Dove Medical Press
Posted: February 21st, 2019, 6:00am GMT
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Global Insulinoma Treatment Market 2019-2023 | Strategic Alliances to Drive Growth | Technavio - Business Wire
Posted: January 9th, 2019, 6:00am GMT
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Blood Sugar Levels & Ranges (Low, Normal & High) Chart - MedicineNet
Posted: January 6th, 2019, 9:13am GMT
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European Medicines Agency Grants Orphan Drug Designation for Xeris' Investigational Ready-to-Use Glucagon for the Treatment of Non-Insulinoma Pancreatogenous Hypoglycaemia Syndrome (NIPHS) - Business Wire
Posted: December 20th, 2018, 6:00am GMT
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In beta-cell regeneration, insulinomas hold 'gold mine' of key genomic data - Healio
Posted: May 18th, 2018, 5:00am GMT
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Diabetes gene found that causes low and high blood sugar levels in the same family - Science Daily
Posted: January 15th, 2018, 6:00am GMT
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Towards β-cell regeneration - Nature.com
Posted: October 23rd, 2017, 5:00am GMT
Towards β-cell regeneration Nature.com -
Pancreatic Neuroendocrine Tumor: Types, Symptoms, Outlook & More - Healthline
Posted: September 27th, 2017, 10:11pm GMT
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Hypoglycemia Symptoms: What Causes It, and More - Healthline
Posted: September 26th, 2017, 4:26am GMT
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Sporadic Insulinoma Presenting as Early Morning Night Terrors - AAP News
Posted: June 1st, 2017, 5:00am GMT
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Cautious Glucose Monitoring in Raynaud's Needed to Avoid Overtreatment - Raynaud's News
Posted: February 1st, 2017, 6:00am GMT
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Diabetes May Be Warning Sign of Pancreatic Cancer - WebMD
Posted: January 31st, 2017, 6:00am GMT
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Pancreatic Cancer Early Symptoms: Recognizing These Signs Of Silent Killer Could Save Your Life - Medical Daily
Posted: November 4th, 2016, 5:00am GMT
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Glucagon-Like Peptide-1 Receptor PET/CT with 68Ga-NOTA-Exendin-4 for Detecting Localized Insulinoma: A Prospective Cohort Study - Journal of Nuclear Medicine
Posted: May 1st, 2016, 5:00am GMT
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Persistent hypoglycemia despite oral therapy - Diabetes - Healio
Posted: March 15th, 2016, 5:00am GMT
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Dr. Donald F. Steiner, Diabetes Researcher, Dies at 84 - New York Times
Posted: November 22nd, 2014, 6:00am GMT
Dr. Donald F. Steiner, Diabetes Researcher, Dies at 84 New York Times -
Woman Acts Drunk in Medical Mystery - ABC News
Posted: July 15th, 2013, 5:00am GMT
Woman Acts Drunk in Medical Mystery ABC News -
Glucagon-like Peptide 1–Receptor Scans to Localize Occult Insulinomas - New England Journal of Medicine (subscription)
Posted: August 14th, 2008, 5:00am GMT
Glucagon-like Peptide 1–Receptor Scans to Localize Occult Insulinomas New England Journal of Medicine (subscription)
PubMed - Insulinoma
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Commentary: Insulinoma-Induced Hypoglycemia with Generalized Chorea, Dystonia, and Ataxia: A Neurological Kaleidoscope
Fetched: September 14th, 2021, 5:01am GMT by Maria Stamelou
Mov Disord Clin Pract. 2021 Sep 3;8(Suppl 1):S9-S10. doi: 10.1002/mdc3.13302. eCollection 2021 Aug.
NO ABSTRACT
PMID:34514035 | PMC:PMC8414494 | DOI:10.1002/mdc3.13302
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Insulinoma-Induced Hypoglycemia with Generalized Chorea, Dystonia, and Ataxia: A Neurological Kaleidoscope
Fetched: September 14th, 2021, 5:01am GMT by Anumeha Mishra
Mov Disord Clin Pract. 2021 Sep 3;8(Suppl 1):S6-S8. doi: 10.1002/mdc3.13287. eCollection 2021 Aug.
NO ABSTRACT
PMID:34514034 | PMC:PMC8414500 | DOI:10.1002/mdc3.13287
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68Ga-Exendin-4 PET/CT Differentiates Insulinoma From Accessory Spleen in a Patient Presenting Indeterminate MRI and 68Ga-DOTATATE PET/CT Findings
Fetched: September 12th, 2021, 5:01am GMT by Yizhen Pang
Clin Nucl Med. 2021 Sep 8. doi: 10.1097/RLU.0000000000003895. Online ahead of print.
ABSTRACT
A 55-year-old woman with endogenous hyperinsulinemia hypoglycemia was clinically diagnosed with insulinoma. Contrast-enhanced MRI revealed an inconclusive hypointense lesion in the pancreatic tail, and the enhancement pattern does not support the diagnosis of insulinoma. 68Ga-DOTATATE PET/CT showed intense radioactivity in this nodule, similar to the radioactivity of the adjacent spleen. Therefore, the diagnosis of accessory spleen cannot be excluded. Follow-up with 68Ga-exendin-4 PET/CT also showed intense uptake in this nodule, but no significant uptake in the spleen was observed at this time. Therefore, the insulinoma was unmasked from the spleen, excluding the diagnosis of accessory spleen, and allowing curative surgery.
PMID:34507334 | DOI:10.1097/RLU.0000000000003895
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TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids
Fetched: September 12th, 2021, 5:01am GMT by Nan Wang
Reprod Biol Endocrinol. 2021 Sep 9;19(1):139. doi: 10.1186/s12958-021-00823-z.
ABSTRACT
BACKGROUND: Granulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3β (Akt/GSK3β) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3β signaling pathway in human GCs.
METHODS: GCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3β signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation.
RESULTS: The average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3β increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3β level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3β as well as FSHR expression whereas E2 synthesis fell.
CONCLUSIONS: During exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3β pathway in human GCs. This response may contribute to inducing oocyte maturation.
PMID:34503515 | PMC:PMC8428109 | DOI:10.1186/s12958-021-00823-z
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68 Ga-DOTATATE PET/CT imaging in endogenous hyperinsulinemic hypoglycemia: A tertiary endocrine centre experience
Fetched: September 10th, 2021, 5:01am GMT by Ravikumar Shah
Clin Endocrinol (Oxf). 2021 Sep 8. doi: 10.1111/cen.14586. Online ahead of print.
ABSTRACT
OBJECTIVE: Literature regarding utility of 68 Ga-DOTATATE PET/CT in insulinoma localization across various subgroups [benign/malignant/multiple endocrine neoplasia-1 (MEN-1) syndrome associated] remains scarce. In this study, the performance of 68 Ga-DOTATATE PET/CT was compared with contrast-enhanced computed tomography (CECT) and 68 Ga-NODAGA-Exendin-4 PET/CT (whenever available) in an endogenous hyperinsulinemic hypoglycemia (EHH) cohort.
DESIGN: Retrospective audit.
PATIENTS: EHH patients [N = 36, lesions (n) = 49, final diagnosis: benign sporadic insulinoma (BSI) (N = 20), malignant insulinoma (N = 4, n = 14), MEN-1 syndrome associated insulinoma (N = 9, n = 15), Munchausen syndrome (N = 2) and drug-induced hypoglycemia (N = 1)] having both preoperative imaging modalities (CECT and 68 Ga-DOTATATE PET/CT).
MEASUREMENTS: Per-lesion sensitivity (Sn) and positive predictive value (PPV) for histopathological diagnosis of insulinoma.
RESULTS: Sn and PPV of 68 Ga-DOTATATE PET/CT were 67.3% and 89.2%; 55% and 100%; 85.7% and 100%; and 66.7% and 77% for overall EHH, BSI, malignant, and MEN-1 syndrome associated insulinoma cohorts respectively. Despite having comparatively lower sensitivity in BSI cohort, 68 Ga-DOTATATE PET/CT localized a pancreatic tail lesion missed by other modalities. 68 Ga-DOTATATE PET/CT had comparatively higher sensitivity in malignant insulinoma than BSI cohort. 68 Ga-DOTATATE PET/CT also paved the way for successful response to 177 Lu-based peptide receptor radionuclide therapy (PRRT). In MEN-1 cases, lower PPV as compared with BSI was due to uptake in non-insulinoma pancreatic neuroendocrine tumours (Pan-NET).
CONCLUSIONS: 68 Ga-DOTATATE PET/CT has supplemental role in selected cases of BSI with negative and/or discordant results with CECT and 68 Ga-NODAGA-Exendin-4 PET/CT. In malignant insulinoma, 68 Ga-DOTATATE-PET/CT has an additional theranostic potential. Interference due to uptake in non-insulinoma Pan-NET in MEN-1 syndrome may hinder insulinoma localization with 68 Ga-DOTATATE-PET/CT.
PMID:34498757 | DOI:10.1111/cen.14586
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Puerarin Inhibits the PERK-eIF2[Formula: see text]-ATF4-CHOP Pathway through Inactivating JAK2/STAT3 Signal in Pancreatic beta-Cells
Fetched: September 8th, 2021, 5:01am GMT by Xiaobo Hu
Am J Chin Med. 2021 Sep 6:1-16. doi: 10.1142/S0192415X21500816. Online ahead of print.
ABSTRACT
Type 1 diabetes (T1D) is an autoimmune and inflammatory disease with excessive loss of pancreatic islet [Formula: see text]-cells. Accumulating evidence indicated that endoplasmic reticulum (ER) stress played a critical role in [Formula: see text]-cells loss, leading to T1D. Therefore, promoting the survival of pancreatic [Formula: see text]cells would be beneficial for patients with T1D. Puerarin is a natural isoflavone that has been demonstrated to be able to decrease blood glucose in patients with T1D. However, it remains unknown whether puerarin improves ER stress to prevent [Formula: see text]-cells from apoptosis. Here, we sought to investigate the role of puerarin in ER stress-associated apoptosis and explore its underlying mechanism in the mouse insulinoma cell line (MIN6). Flow cytometry and cell counting kit-8 (CCK8) experiments showed that puerarin caused a significant increase in the viability of MIN6 cells injured by H2O2. Furthermore, the protein kinase R-like ER kinase (PERK) signal pathway, a critical branch of ER stress response, was found to be involved in this process. Puerarin inhibited the phosphorylation of PERK, subsequently suppressed the phosphorylation of eukaryotic initiation factor 2[Formula: see text] (eIF2[Formula: see text], then decreased the activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression, ultimately attenuating ER stress to prevent MIN6 cells from apoptosis. In addition, puerarin inhibited the activation of Janus kinase 2 (JAK2)/signal transducer and activators of transcription 3 (STAT3), which suppressed the PERK signal cascade with decreased ATF4 and CHOP levels. Taken together, our results firstly demonstrated that puerarin could prevent MIN6 cells from apoptosis at least in part by inhibiting the PERK-eIF2[Formula: see text]-ATF4-CHOP axis under ER stress conditions, which might be mediated by inactivation of the JAK2/STAT3 signal pathway. Therefore, investigating the mechanism underlying the effects of puerarin might highlight the potential roles of puerarin developing into an antidiabetic drug.
PMID:34488550 | DOI:10.1142/S0192415X21500816
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A case of fulminant type 1 diabetes mellitus in an elderly patient who developed cardiopulmonary arrest from diabetic ketoacidosis and whose imaging course was monitored
Fetched: September 8th, 2021, 5:01am GMT by Yasunari Yoshida
Nihon Ronen Igakkai Zasshi. 2021;58(3):482-488. doi: 10.3143/geriatrics.58.482.
ABSTRACT
A 71-year-old man with a history of hypertension and nephrosclerosis visited a primary care doctor for a regular visit. After a few days of vomiting and diarrhea, gastroenteritis was suspected and he was prescribed medication for these symptoms by his previous doctor. The next morning, he visited our hospital complaining of malaise and abdominal distention.The patient's blood glucose level was 1,385 mg/dL, his arterial blood pH was 6.885 (followed by an elevated serum ketone level), and hyperkinesis from diabetic ketoacidosis (DKA) was observed. The patient had experienced cardiopulmonary arrest, likely due to ventricular fibrillation. After cardiopulmonary resuscitation, the patient was admitted to hospital and treated for DKA. The urinary and serum C-peptide levels were below the limit of sensitivity, and anti-glutamic acid decarboxylase antibody and anti-insulinoma-associated antigen-2 antibody were not detected in the serum. These findings were consistent with a diagnosis of fulminant type 1 diabetes mellitus. We herein report a rare case of resuscitation in an elderly patient with fulminant-onset type 1 diabetes mellitus. We carefully observed the imaging history of the patient with great interest.
PMID:34483177 | DOI:10.3143/geriatrics.58.482
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Current status and future prospects of PET-imaging applications in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs)
Fetched: September 6th, 2021, 5:01am GMT by Georgios Z Papadakis
Eur J Radiol. 2021 Aug 25;143:109932. doi: 10.1016/j.ejrad.2021.109932. Online ahead of print.
ABSTRACT
Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of rare neoplasms with increasing incidence over the last decades. Localization of GEP-NETs and their metastases is a vital component for the implementation of accurate and patient-tailored treatment strategies. Addressing this challenge requires the employment of multidisciplinary imaging approaches, with hybrid positron emission tomography/computed tomography (PET/CT) imaging techniques standing at the forefront of this effort. GEP-NETs exhibit several pathophysiologic characteristics, which can serve as highly specific molecular targets that can be effectively visualized and quantified by means of PET-radiopharmaceuticals, facilitating diagnosis, accurate staging and efficient monitoring of treatment response. Furthermore, the capability for whole-body, in-vivo, non-invasive characterization of the molecular heterogeneity of the disease, provides strong prognostic information, while enabling the selection of patients suitable for precision-based theranostic approaches. The dual tracer (18F-FDG & 68Ga-DOTA-peptides) PET/CT imaging approach is the current optimal diagnostic imaging strategy, since it enables tumor localization, accurate staging, non-invasive whole-body total tumor burden characterization of disease heterogeneity, while providing strong prognostic information and guidance towards treatment strategy. Moreover, 64Cu-DOTATATE has been recently approved by FDA for SSTRs positive NETs, promising substantial diagnostic and logistical benefits. Furthermore, 18F-DOPA offers diagnostic capabilities for serotonin-secreting GEP-NETs which are not characterized by cell-surface over-expression of somatostatin receptors (SSTRs) and cannot be seen on morphological imaging. In addition, PET/CT with agents targeting the expression of glucagon-like peptide-1 receptor (GLP-R1) should be considered in cases of clinical suspicion for insulinomas that cannot be detected by morphological imaging or STTRs PET/CT imaging.
PMID:34482177 | DOI:10.1016/j.ejrad.2021.109932
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Use of Selective Arterial Calcium Stimulation Testing in Identification of Insulinoma in a Patient After Bariatric Surgery
Fetched: September 5th, 2021, 5:01am GMT by Julianne M Szczepanski
Lab Med. 2021 Sep 4:lmab071. doi: 10.1093/labmed/lmab071. Online ahead of print.
ABSTRACT
OBJECTIVE: Insulinomas are rare in the post-bariatric surgery setting. The differential diagnosis for hypoglycemia is broad, requiring laboratory testing to verify endogenous hyperinsulinemic hypoglycemia. Selective arterial calcium stimulation testing (SACST) can help localize abnormal insulin production. We describe a patient with histologically confirmed insulinoma after bariatric surgery diagnosed with the aid of SACST.
METHODS: We present a 67 year old woman with a history of Roux-en-Y bypass surgery who presented with endogenous hyperinsulinemic hypoglycemia. Initially, no pancreatic lesion was identified radiologically. We pursued SACST to localize the source of insulin production.
RESULTS: The SACST successfully localized the source of hyperfunctioning islet cells to the pancreatic tail with absolute insulin values in a range consistent with insulinoma. Additional radiologic studies showed a small tumor in the pancreatic tail. Pathology showed a well-differentiated neuroendocrine tumor, compatible with insulinoma.
CONCLUSION: This case study illustrates the usefulness of SACST for the diagnosis and localization of insulinoma.
PMID:34480182 | DOI:10.1093/labmed/lmab071
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Primary small cell neuroendocrine carcinoma in the nasal cavity: A CARE-compliant case report
Fetched: September 4th, 2021, 5:01am GMT by Li-Yu Chen
Medicine (Baltimore). 2021 Sep 3;100(35):e27136. doi: 10.1097/MD.0000000000027136.
ABSTRACT
RATIONALE: Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses is a rare but aggressive neoplasm with a poor prognosis and a strong propensity for regional recurrence and distant metastasis. Diagnosis is challenging and relies on immunohistochemical study. Treatment includes surgical resection, radiation therapy, chemotherapy, or a combination of these modalities. However, the optimal therapeutic strategy is still controversial. Due to its rarity, the complexity of the histological diagnosis, and the variety of the treatment regimens, we presented a case of primary small cell neuroendocrine carcinoma in the nasal cavity with description of the clinical manifestation, pathology features, and our treatment regimen.
PATIENT CONCERNS: An 82-year-old female patient with hypertension presented with right epistaxis on and off with nasal obstruction for several days.
DIAGNOSIS: An exophytic mass over the posterior end of the right inferior turbinate was found on nasopharyngoscope. Biopsy was done and the pathology confirmed small cell carcinoma, strongly positive for cytokeratin (AE1/AE3) and insulinoma-associated protein 1 (INSM-1), scatteredly positive for chromogranin A, synaptophysin and CD56. The final diagnosis was small cell neuroendocrine carcinoma of right nasal cavity, pT1N0M0, stage I.
INTERVENTIONS: The patient underwent wide excision of right intra-nasal tumor and post-operative radiotherapy with a dose of 6600 cGy in 33 fractions.
OUTCOMES: No local recurrence or distant metastasis was noted during the 12 months of follow-up.
LESSONS: Multimodality treatment remains the most common therapeutic strategy, although no proven algorithm has been established due to the rarity of this disease. Further investigation is needed for providing evidence to standardize the treatment protocol.
PMID:34477164 | PMC:PMC8415994 | DOI:10.1097/MD.0000000000027136
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In vitro cytoprotective activity of cyanidin 3-glucoside extracts from Haematocarpus validus pomace on streptozotocin induced oxidative damage in pancreatic β-cells
Fetched: September 2nd, 2021, 5:01am GMT by Raju Sasikumar
Saudi J Biol Sci. 2021 Sep;28(9):5338-5348. doi: 10.1016/j.sjbs.2021.05.065. Epub 2021 May 29.
ABSTRACT
Cyanidin-3-glucoside (C3Ghv) compounds were purified and isolated from the anthocyanins extract of Haematocarpus validus. C3Ghv were studied for antioxidant and cytoprotective properties on pancreatic β-cells of rat insulinoma cells (RINm5F) against the oxidative stress induced by streptozotocin (STZ). The exposure of RINm5F cells to C3Ghv at concentration of 100 and 200 μg/mL for 24 h reduced 10% and 23% cell viability, respectively, as compared to control cells. The pre-treatment of RINm5F cells with C3Ghv (50 µg/mL) increased the cell viability by 29% as compared to control, on being treated with STZ (10 mM) for 24 h. The pre-treatment of RINm5F cells with C3Ghv (50 µg/mL) for 24 h followed by exposure to STZ (10 mM) for 1 h decreased the generation of reactive oxygen species (ROS) by 57%, generation of nitric oxide by 22.8%, generation of malondialdehyde (MDA) by 32%, the production of p-ERK ½ by 83%, p-JNK by 82.6%, p-MEK by 57%, and p-p38 MAPK by 64%. The C3Ghv treatment also decreased the ratio of apoptotic proteins Bax to Bcl-2 by 61%, and improved the M2 phase of cell cycle by 75% as compared to STZ treated cells. The overall results suggest that C3Ghv protects pancreatic β-cells against oxidative stress-induced apoptosis, thereby implicating the significant role of C3Ghv as an antidiabetic agent.
PMID:34466113 | PMC:PMC8381084 | DOI:10.1016/j.sjbs.2021.05.065
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Regulation and function of AP-1 in insulinoma cells and pancreatic beta-cells
Fetched: September 1st, 2021, 5:01am GMT by Tobias M Backes
Biochem Pharmacol. 2021 Aug 27;193:114748. doi: 10.1016/j.bcp.2021.114748. Online ahead of print.
ABSTRACT
Cav1.2 L-type voltage-gated Ca2+ channels play a central role in pancreatic β-cells by integrating extracellular signals with intracellular signaling events leading to insulin secretion and altered gene transcription. Here, we investigated the intracellular signaling pathway following stimulation of Cav1.2 Ca2+ channels and addressed the function of the transcription factor activator protein-1 (AP-1) in pancreatic β-cells of transgenic mice. Stimulation of Cav1.2 Ca2+ channels activates AP-1 in insulinoma cells. Pharmacological and genetic experiments identified c-Jun N-terminal protein kinase as a signal transducer connecting Cav1.2 Ca2+ channel activation with gene transcription. Moreover, the basic region-leucine zipper proteins ATF2 and c-Jun or c-Jun-related proteins were involved in stimulus-transcription coupling. We addressed the functions of AP-1 in pancreatic β-cells analyzing a newly generated transgenic mouse model. These transgenic mice expressed A-Fos, a mutant of c-Fos that attenuates DNA binding of c-Fos dimerization partners. In insulinoma cells, A-Fos completely blocked AP-1 activation following stimulation of Cav1.2 Ca2+ channels. The analysis of transgenic A-Fos-expressing mice revealed that the animals displayed impaired glucose tolerance. Thus, we show here for the first time that AP-1 controls an important function of pancreatic β-cells in vivo, the regulation of glucose homeostasis.
PMID:34461116 | DOI:10.1016/j.bcp.2021.114748
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Sub-stoichiometric inhibition of IAPP aggregation: a peptidomimetic approach to anti-amyloid agents
Fetched: August 31st, 2021, 5:01am GMT by Debabrata Maity
RSC Chem Biol. 2020 Aug 19;1(4):225-232. doi: 10.1039/d0cb00086h. eCollection 2020 Oct 1.
ABSTRACT
Membrane-catalysed misfolding of islet amyloid polypeptide is associated with the death of β-cells in type II diabetes (T2D). Most active compounds so far reported require high doses for inhibition of membrane bound IAPP fibrillation. Here, we describe a naphthalimide-appended oligopyridylamide-based α-helical mimetic, DM 1, for targeting membrane bound IAPP. DM 1 completely inhibits the aggregation of IAPP at doses of 0.2 equivalents. DM 1 is also effective at similarly low doses for inhibition of seed-catalyzed secondary nucleation. An NMR based study demonstrates that DM 1 modulates IAPP self-assembly by stabilizing and/or perturbing the N-terminus helix conformation. DM 1 at substoichiometric doses rescues rat insulinoma cells from IAPP-mediated cytotoxicity. Most importantly, 0.2 equivalents of DM 1 disaggregate preformed oligomers and fibrils and can reverse cytotoxicity by modulating toxic preformed oligomers and fibrils of IAPP into non-toxic conformations.
PMID:34458762 | PMC:PMC8341728 | DOI:10.1039/d0cb00086h
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Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes
Fetched: August 29th, 2021, 5:01am GMT by Pavel H Lugo-Fabres
Biomedicines. 2021 Aug 1;9(8):936. doi: 10.3390/biomedicines9080936.
ABSTRACT
The FDA's approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from Conus species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the CaV1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic β-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas's capability to produce insulin is still effective.
PMID:34440140 | PMC:PMC8391312 | DOI:10.3390/biomedicines9080936
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Small peptide-based GLP-1R ligands: an approach to reduce the kidney uptake of radiolabeled GLP-1R-targeting agents?
Fetched: August 26th, 2021, 5:01am GMT by Veronika Barbara Felber
EJNMMI Radiopharm Chem. 2021 Aug 25;6(1):29. doi: 10.1186/s41181-021-00136-x.
ABSTRACT
AIM: Elevated kidney uptake in insulinoma patients remains a major limitation of radiometallated exendin-derived ligands of the glucagon-like peptide 1 receptor (GLP-1R). Based on the previously published potent GLP-1R-activating undecapeptide 1, short-chained GLP-1R ligands were developed to investigate whether kidney uptake can be reduced by means of direct 18F-labeling (nuclide-based accelerated renal excretion) or the reduction of the overall ligand charge (ligand-based reduced kidney uptake).
MATERIALS & METHODS: GLP-1R ligands were prepared according to optimized standard protocols via solid-phase peptide synthesis (SPPS) or, when not practicable, via fragment coupling in solution. Synthesis of (2'-Et, 4'-OMe)4, 4'-L-biphenylalanine ((2'-Et, 4'-OMe)BIP), required for the preparation of 1, was accomplished by Suzuki-Miyaura cross-coupling. In vitro experiments were performed using stably transfected GLP-1R+ HEK293-hGLP-1R cells.
RESULTS: In contrast to the three reference ligands glucagon-like peptide 1 (GLP-1, IC50 = 23.2 ± 12.2 nM), [Nle14, Tyr(3-I)40]exendin-4 (IC50 = 7.63 ± 2.78 nM) and [Nle14, Tyr40]exendin-4 (IC50 = 9.87 ± 1.82 nM), the investigated GLP-1R-targeting small peptides (9-15 amino acids), including lead peptide 1, exhibited only medium to low affinities (IC50 > 189 nM). Only SiFA-tagged undecapeptide 5 (IC50 = 189 ± 35 nM) revealed a higher affinity than 1 (IC50 = 669 ± 242 nM).
CONCLUSION: The investigated small peptides, including lead peptide 1, could not compete with favorable in vitro characteristics of glucagon-like peptide 1 (GLP-1), [Nle14, Tyr(3-I)40]exendin-4 and [Nle14, Tyr40]exendin-4. The auspicious EC50 values of 1 provided by the literature could not be transferred to competitive binding experiments. Therefore, the use of 1 as a basic scaffold for the design of further GLP-1R-targeting radioligands cannot be recommended. Further investigations might include the scaffold of 5, although substantial optimizations concerning affinity and lipophilicity would be required. In sum, GLP-1R-targeting radioligands with reduced kidney uptake could not be obtained in this work, which emphasizes the need for further ligands addressing this particular issue.
PMID:34432147 | PMC:PMC8387526 | DOI:10.1186/s41181-021-00136-x
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Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer
Fetched: August 26th, 2021, 5:01am GMT by Kaushal Asrani
J Pathol. 2021 Aug 24. doi: 10.1002/path.5781. Online ahead of print.
ABSTRACT
Neuroendocrine prostate cancer (NEPC) is a rare but aggressive histologic variant of prostate cancer that responds poorly to androgen deprivation therapy. Hybrid NEPC-adenocarcinoma (AdCa) tumors are common, often eluding accurate pathologic diagnosis and requiring ancillary markers for classification. We recently performed an outlier-based meta-analysis across a number of independent gene expression microarray datasets to identify novel markers that differentiate NEPC from AdCa, including up-regulation of Insulinoma-associated protein 1 (INSM1) and loss of Yes-associated protein 1 (YAP1). Here, using diverse cancer gene expression datasets, we show that Hippo pathway-related genes, including YAP1, are among the top down-regulated gene sets with expression of the neuroendocrine transcription factors, including INSM1. In prostate cancer cell lines, transgenic mouse models and human prostate tumor cohorts, we confirm that YAP1 RNA and YAP1 protein expression are silenced in NEPC and demonstrate that the inverse correlation of INSM1 and YAP1 expression helps to distinguish AdCa from NEPC. Mechanistically, we find that YAP1 loss in NEPC may help to maintain INSM1 expression in prostate cancer cell lines and we further demonstrate that YAP1 silencing likely occurs epigenetically, via CpG hypermethylation near its transcriptional start site. Taken together, these data nominate two additional markers to distinguish NEPC from AdCa and add to data from other tumor types suggesting that Hippo signaling is tightly reciprocally regulated with neuroendocrine transcription factor expression. This article is protected by copyright. All rights reserved.
PMID:34431104 | DOI:10.1002/path.5781
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Factitious Hypoglycemia
Fetched: August 22nd, 2021, 5:01am GMT by Dana H. Awad
2021 Jul 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.
ABSTRACT
Factitious hypoglycemia is the intentional attempt to induce low blood glucose levels. It remains one of the diagnostic challenges that endocrinologists face during their practice and usually leads to costly, unnecessary investigations to rule out other causes of hypoglycemia.
When insulin is self-injected, laboratory studies will show high plasma insulin levels in combination with low plasma C-peptide levels during the hypoglycemic episode. With sulfonylurea consumption, the clinical picture may mimic an insulinoma with high plasma levels of both C-peptide and insulin; a positive drug screen can render the diagnosis.
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Unusual presentation of an insulinoma in an elderly male patient
Fetched: August 22nd, 2021, 5:01am GMT by M Adarsh
J Postgrad Med. 2021 Jul-Sep;67(3):164-167. doi: 10.4103/jpgm.JPGM_1165_20.
ABSTRACT
Insulinoma is a rare neuroendocrine tumor originating from hypersecreting beta-cells of islets of Langerhans in the pancreas. We report a case of 72-year-old male, with chronic alcohol abuse, presenting with atypical features like refractory recurrent secondary generalized seizures and behavioral disturbances with increased irritability, initially mistreated as alcohol withdrawal. Detailed history, particularly the relationship of the symptoms with food intake, made us think of other causes of seizures. Fasting biochemical investigations and localizing studies helped clinch the diagnosis. The tumor was localized with the help of endoscopic ultrasonography and whole-body Ga68-DOTANOC PET-CT. The patient was treated conservatively with diazoxide and is doing well on follow-up. The present case report emphasizes the importance of detailed clinical history, more so in atypically presenting cases of refractory seizures. Insulinoma can be medically managed despite surgery being the gold standard curative treatment.
PMID:34414928 | DOI:10.4103/jpgm.JPGM_1165_20
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Long-term morbidity and mortality in patients diagnosed with an insulinoma
Fetched: August 11th, 2021, 5:01am GMT by Elina Peltola
Eur J Endocrinol. 2021 Sep 1;185(4):577-586. doi: 10.1530/EJE-21-0230.
ABSTRACT
OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort.
DESIGN: Retrospective cohort study.
METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses.
RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years).
CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.
PMID:34374651 | DOI:10.1530/EJE-21-0230
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Multiple Endocrine Neoplasia Type 1 with Concomitant Existence of Malignant Insulinoma: A Rare Finding
Fetched: August 10th, 2021, 5:01am GMT by Randhir Sagar Yadav
Case Rep Endocrinol. 2021 Jul 28;2021:8842667. doi: 10.1155/2021/8842667. eCollection 2021.
ABSTRACT
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome of autosomal dominant inheritance defined by co-occurrence of two or more tumors originating from the parathyroid gland, pancreatic islet cells, and/or anterior pituitary. Insulinoma which has an incidence of 0.4% is a rare pancreatic neuroendocrine tumor. Malignant insulinoma is extremely rare, while primary hyperparathyroidism is a common occurrence in MEN1. We present a case of MEN1 syndrome with 2.6 cm insulinoma in the pancreatic head and parathyroid adenoma in a 56-year-old female who presented with symptoms suggestive of hypoglycemia like multiple episodes of loss of consciousness for four years. Classical pancreaticoduodenectomy was carried out, and the postoperative period was uneventful. Later, subtotal parathyroidectomy was performed, which showed parathyroid adenoma. Patients presenting with features of hypoglycemia should be vigilantly assessed for the presence of a sinister pathology.
PMID:34367700 | PMC:PMC8337156 | DOI:10.1155/2021/8842667
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Alternative lengthening of telomeres phenotype predicts progression risk in non-insulinomas in a Chinese cohort
Fetched: August 5th, 2021, 5:02am GMT by Xinchao Ban
Neuroendocrinology. 2021 Jul 12. doi: 10.1159/000518413. Online ahead of print.
NO ABSTRACT
PMID:34348341 | DOI:10.1159/000518413
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Clinical characteristics and incidences of benign and malignant insulinoma using a national inpatient database in Japan
Fetched: August 4th, 2021, 5:01am GMT by Kayo Ikeda Kurakawa
J Clin Endocrinol Metab. 2021 Aug 3:dgab559. doi: 10.1210/clinem/dgab559. Online ahead of print.
ABSTRACT
CONTEXT: Insulinoma is the most common pancreatic functional neuroendocrine neoplasm, yet little information on recent clinical practice in patients with insulinoma, especially malignant insulinoma, is available.
OBJECTIVE: To clarify the characteristics and practice patterns in patients with insulinoma using a national inpatient database.
METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with insulinoma admitted between 2010 and 2018. We compared background characteristics and therapeutic interventions between patients with benign and malignant insulinoma. We also estimated the incidence of insulinoma using the number of patients with newly diagnosed insulinoma in 2012.
RESULTS: We identified 844 patients with benign insulinoma and 102 patients with malignant insulinoma. Patients with malignant insulinoma were younger (median, 55.5 vs. 66.0 years, P < 0.001) and less likely to be female (55.9% vs. 65.3%, P = 0.061) than patients with benign insulinoma. Analysis of therapeutic interventions revealed that patients with malignant insulinoma more frequently received medications (71.6% vs. 49.6%, P < 0.001) but less frequently underwent pancreatic surgery (57.8% vs. 72.0%, P = 0.003). Older patients were a smaller proportion of those undergoing surgery and a larger proportion of those managed with medications without surgery (P < 0.001). The incidence of insulinoma was estimated to be 3.27 (95% confidence interval, 2.93-3.61) persons per million Japanese adult population per year.
CONCLUSIONS: The present study using a nationwide database had a larger sample size than previous studies and revealed definitive differences in patient characteristics and therapeutic patterns between benign and malignant insulinoma.
PMID:34343300 | DOI:10.1210/clinem/dgab559
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Simplifying prediction of disease progression in pre-symptomatic type 1 diabetes using a single blood sample
Fetched: August 3rd, 2021, 5:02am GMT by Naiara G Bediaga
Diabetologia. 2021 Aug 2. doi: 10.1007/s00125-021-05523-2. Online ahead of print.
ABSTRACT
AIMS/HYPOTHESIS: Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw.
METHODS: Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial-Type 1, The Environmental Determinants of Diabetes in the Young [1]) and in a general population of Bavarian children who participated in Fr1da.
RESULTS: Cox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA1c and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. In TrialNet, the AUC for receiver operating characteristic curves for models named M60, M90 and M120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TEDDY, where only 120 min blood sampling had been performed, the M120 AUC was 0.865. In Fr1da, the M120 AUC of 0.742 was significantly greater than the M60 AUC of 0.615.
CONCLUSIONS/INTERPRETATION: Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. The operational simplicity of M120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M120 could be readily applied to decrease the cost and complexity of risk stratification.
PMID:34338806 | DOI:10.1007/s00125-021-05523-2
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Mutant Huntingtin Impairs Pancreatic β-cells by Recruiting IRS-2 and Disturbing the PI3K/AKT/FoxO1 Signaling Pathway in Huntington's Disease
Fetched: August 1st, 2021, 5:01am GMT by Li Li
J Mol Neurosci. 2021 Jul 31. doi: 10.1007/s12031-021-01869-9. Online ahead of print.
ABSTRACT
Patients with Huntington's disease (HD) have an increased incidence of diabetes. However, the molecular mechanisms of pancreatic β-cell dysfunction have not been entirely clarified. Revealing the pathogenesis of diabetes can provide a novel understanding of the onset and progression of HD, as well as potential clues for the development of new therapeutics. Here, we demonstrated that the mouse pancreatic insulinoma cell line NIT-1 expressing N-terminal mutant huntingtin (mHTT) containing 160 polyglutamine (160Q cells) displayed lower cell proliferative ability than the cells expressing N-terminal wild-type HTT containing 20 polyglutamine (20Q cells). In addition, 160Q cells were more prone to apoptosis and exhibited deficient glucose-stimulated insulin expression and secretion. Furthermore, insulin signaling molecule insulin receptor substrate 2 (IRS-2) expression decreased and was recruited into mHTT aggregates. Consequently, glucose stimulation failed to activate the downstream molecule phosphatidylinositol-3 kinase (PI3K) in 160Q cells, leading to reduced phosphorylation levels of serine-threonine protein kinase AKT and forkhead box protein O1 (FoxO1). These data indicate that activation of the glucose-stimulated PI3K/AKT/FoxO1 signaling pathway is significantly blocked in pancreatic β-cells in HD. Importantly, insulin treatment inhibited the aggregation of mHTT and significantly improved the activation of PI3K/AKT/FoxO1 signaling in 160Q cells. These results suggest that the inhibition of the PI3K/AKT/FoxO1 pathway might be due to the recruitment of IRS-2 into mHTT aggregates in HD β-cells, ultimately contributing to the impairment of pancreatic β-cells. In conclusion, our work provides new insight into the underlying mechanisms of the high incidence of diabetes and abnormal glucose homeostasis in HD.
PMID:34331233 | DOI:10.1007/s12031-021-01869-9