7,011 results match your criteria Insulinoma


Insulinoma resembling a rapid eye movement sleep behavior disorder: a case report.

Int Med Case Rep J 2019 21;12:51-54. Epub 2019 Feb 21.

Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan,

Some patients with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed with psychiatric disease. We present the case of a 72-year-old Japanese female who exhibited violent behavior while asleep and received a diagnosis of suspected rapid eye movement sleep behavior disorder (RBD). She was admitted to the psychiatry ward after receiving levomepromazine 25 mg intramuscularly. Read More

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http://dx.doi.org/10.2147/IMCRJ.S200489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391156PMC
February 2019
2 Reads

Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation.

Mol Cell Endocrinol 2019 Mar 7. Epub 2019 Mar 7.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. Electronic address:

Severe inflammation in the islets is observed in obese patients with type 2 diabetes. Inflammation in the islets is caused by obesity-induced serum free fatty acids. Asprosin is a fasting-induced adipokine, which contributes to hepatic glucose production. Read More

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http://dx.doi.org/10.1016/j.mce.2019.03.001DOI Listing

Distinct clinicopathological and prognostic features of insulinoma with synchronous distant metastasis.

Pancreatology 2019 Mar 1. Epub 2019 Mar 1.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 20032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China; Shanghai Pancreatic Cancer Institute, Shanghai, 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China. Electronic address:

Background: The clinicopathological and prognostic features of insulinoma with synchronous metastases are unclear. This study aimed to verify the distinct clinicopathological and prognostic features of insulinoma with synchronous distant metastasis.

Methods: Patients with pancreatic neuroendocrine tumor (PanNET) were retrospectively enrolled and divided into cohort 1 (Fudan University Shanghai Cancer Center) and cohort 2 (Surveillance, Epidemiology, and End Results Program database). Read More

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http://dx.doi.org/10.1016/j.pan.2019.02.011DOI Listing
March 2019
1 Read

Genetic obesity increases pancreatic expression of mitochondrial proteins which regulate cholesterol efflux in BRIN-BD11 insulinoma cells.

Biosci Rep 2019 Feb 28. Epub 2019 Feb 28.

Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, United Kingdom

Pancreatic β-cells are sensitive to fluctuations in cholesterol content, which can damage the insulin secretion pathway, contributing to the aetiology of type 2 diabetes mellitus.   Cholesterol efflux to (apo)lipoproteins, via ATP binding cassette transporter A1 (ABCA1), can prevent intracellular cholesterol accumulation; in some peripheral cells, ABCA1-dependent efflux is enhanced by promotion of cholesterol trafficking to, and generation of Liver X receptor (LXR) ligands by, mitochondrial sterol 27-hydroxylase (Cyp27A1) and its redox partners, adrenodoxin (ADX) and adrenodoxin reductase (ADXR).  Despite this, the roles of mitochondrial cholesterol trafficking (steroidogenic acute regulatory protein [StAR] and 18kDa translocator protein [TSPO]) and metabolizing proteins in insulin-secreting cells remain wholly uncharacterised. Read More

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http://bioscirep.org/lookup/doi/10.1042/BSR20181155
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http://dx.doi.org/10.1042/BSR20181155DOI Listing
February 2019
1 Read

Transarterial Embolization for Mitigation of Severe Hypoglycemia in 2 Patients with Primary Pancreatic Insulinoma.

J Vasc Interv Radiol 2019 Mar;30(3):476-479

Department of Radiology, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, United Kingdom.

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https://linkinghub.elsevier.com/retrieve/pii/S10510443183168
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http://dx.doi.org/10.1016/j.jvir.2018.10.032DOI Listing
March 2019
4 Reads
2.149 Impact Factor

Medical Therapy in Patients with Endogenous Hypoglycaemia: is Euglycaemia Achievable?

Clin Endocrinol (Oxf) 2019 Feb 28. Epub 2019 Feb 28.

Service d'Endocrinologie, Maladies Métaboliques et Nutrition et Institut CardioMet, Centre Hospitalier Universitaire Rangueil-Larrey, 24 chemin de Pouvourville, 31059, Toulouse Cedex 9, France.

Context: While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalise plasma glucose levels can be useful.

Objective: The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo- or hyperglycaemic excursions.

Patients And Methods: All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enrolled and underwent a six-day continuous glucose monitoring (CGM) recording. Read More

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http://dx.doi.org/10.1111/cen.13961DOI Listing
February 2019
1 Read

Usefulness of hemoglobin A1c and glycated albumin measurements for insulinoma screening: an observational case-control study.

BMC Cancer 2019 Feb 26;19(1):174. Epub 2019 Feb 26.

Department of Internal Medicine, Hakuhokai Central Hospital, Hyogo, 669-0953, Japan.

Background: Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Read More

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http://dx.doi.org/10.1186/s12885-019-5389-7DOI Listing
February 2019
2 Reads

Alleles of Insm1 determine whether RIP1-Tag2 mice produce insulinomas or nonfunctioning pancreatic neuroendocrine tumors.

Oncogenesis 2019 Feb 22;8(3):16. Epub 2019 Feb 22.

Raymond and Beverly Sackler Foundation Laboratory, New Brunswick, NJ, USA.

The two most common types of pancreatic neuroendocrine tumors (PanNETs) are insulinomas and nonfunctioning PanNETs (NF-PanNETs). Insulinomas are small, rarely metastatic tumors that secrete high amounts of insulin, and nonfunctioning PanNETs are larger tumors that are frequently metastatic but that do not secrete hormones. Insulinomas are modeled by the highly studied RIP1-Tag2 (RT2) transgenic mice when bred into a C57Bl/6 (B6) genetic background (also known as RT2 B6 mice). Read More

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http://dx.doi.org/10.1038/s41389-019-0127-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386750PMC
February 2019

Pancreatic autoantibodies and CD14+CD16+ monocytes subset are associated with the impairment of ß-cell function after simultaneous pancreas-kidney transplantation.

PLoS One 2019 22;14(2):e0212547. Epub 2019 Feb 22.

Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.

Pancreatic autoantibodies (AAb) has been associated with a worse pancreas graft survival after simultaneous pancreas-kidney transplantation (SPK). However, due to the variable time for AAb to become positive and the lack of early biomarkers suggesting such autoimmune activation, the mechanisms leading ß-cell destruction remain uncertain. The present study aimed to evaluate the association between post-transplant AAb and the functional impairment of the pancreatic ß-cell and also the association of such AAb with inflammation after SPK. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212547PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386378PMC
February 2019
1 Read

Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells.

In Vitro Cell Dev Biol Anim 2019 Feb 21. Epub 2019 Feb 21.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.

The mechanism whereby 17β-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10 to 1 × 10 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. Read More

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http://dx.doi.org/10.1007/s11626-019-00328-5DOI Listing
February 2019
2 Reads

Metastatic Insulinoma Controlled by Targeted Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Solitary Kidney and MEN-1 Syndrome.

Clin Nucl Med 2019 Feb 15. Epub 2019 Feb 15.

From the Departments of Nuclear Medicine.

A 54-year-old man with multiple endocrine neoplasia type 1 had previous history of parathyroid surgery and left thyroid lobectomy 5 years earlier, and was referred for recurrent hypoglycemic episodes. Ga-DOTATATE PET/CT had showed multiple lesions in the right lung, liver, and pancreas. Biopsy from pancreas revealed low-grade neuroendocrine neoplasia. Read More

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http://dx.doi.org/10.1097/RLU.0000000000002500DOI Listing
February 2019
2 Reads
3.931 Impact Factor

Prevalence of diabetes and presence of autoantibodies against zinc transporter 8 and glutamic decarboxylase at diagnosis and at follow up of Graves' disease.

Endocrine 2019 Feb 19. Epub 2019 Feb 19.

Department of Endocrinology, Lund University, SE-221 00, Lund, Sweden.

Purpose: The aim of this work was to investigate, in patients with newly diagnosed Graves' disease (GD), the frequency of islet autoantibodies including autoantibodies against Zink transporter 8 (ZnT8A), as well as to investigate the relation between thyroid autoantibodies, islet autoantibodies and diabetes both before GD diagnosis and at follow-up.

Methods: Blood samples from 278 patients with newly diagnosed GD were analyzed for autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA2-A), three variants of zinc transporter 8 (ZnT8A), thyroid peroxidase (TPOA) and the TSH receptor (TRAb). Information on other autoimmune diseases, as well as development of diabetes during follow up was gathered from patient's medical journal. Read More

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http://dx.doi.org/10.1007/s12020-019-01852-wDOI Listing
February 2019
2 Reads

Oleic acid protects insulin-secreting INS-1E cells against palmitic acid-induced lipotoxicity along with an amelioration of ER stress.

Endocrine 2019 Feb 18. Epub 2019 Feb 18.

Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, Endocrinology Department, West China Hospital, Sichuan University, Chengdu, P.R. China.

Purpose: It is demonstrated that unsaturated fatty acids can counteract saturated fatty acids-induced lipotoxicity, but the molecular mechanisms are unclear. In this study, we investigated the protective effects of monounsaturated oleic acid (OA) against saturated palmitic acid (PA)-induced cytotoxicity in rat β cells as well as islets, and mechanistically focused on its regulation on endoplasmic reticulum (ER) stress.

Methods: Rat insulinoma cell line INS-1E cells and primary islets were treated with PA with or without OA for 24 h to determine the cell viability, apoptosis, and ER stress. Read More

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http://dx.doi.org/10.1007/s12020-019-01867-3DOI Listing
February 2019
1 Read

Determining the insulin secretion potential for certain specific G-protein coupled receptors in MIN6 pancreatic beta cells

Turk J Med Sci 2019 Feb 11;49(1):403-411. Epub 2019 Feb 11.

Background/aim: The polypeptide hormone insulin is essential for the maintenance of whole-body fuel homeostasis, and defects in insulin secretion and/or action are associated with the development of type 1 and type 2 diabetes. The aim of this study was to assess the role of some G-protein coupled receptors (GPCRs), GPR54, GPR56, and GPR75, and cannabinoid receptors CB1R and CB2R, in the regulation of pancreatic β-cell function.

Materials And Methods: Insulin secretion from mouse insulinoma β-cell line (MIN6) monolayers was assessed via insulin radioimmu-noassay (RIA). Read More

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http://dx.doi.org/10.3906/sag-1712-147DOI Listing
February 2019
2 Reads

5'-Iodotubercidin represses expression, decreases cAMP levels, and suppresses human neuroblastoma cell growth.

J Biol Chem 2019 Feb 12. Epub 2019 Feb 12.

Departments of Pediatrics and Genetics, LSU Health Sciences Center, United States.

Insulinoma associated-1 (INSM1) is a key protein functioning as a transcriptional repressor in neuroendocrine differentiation and is activated by N-Myc in human neuroblastoma (NB). INSM1 modulates the phosphoinositide 3-kinase (PI3K)-AKT Ser/Thr kinase (AKT)-glycogen synthase kinase 3β (GSK3β) signaling pathway through a positive-feedback loop, resulting in N-Myc stabilization. Accordingly, INSM1 has emerged as a critical player closely associated with N-Myc in facilitating NB cell growth. Read More

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http://dx.doi.org/10.1074/jbc.RA118.006761DOI Listing
February 2019
2 Reads

The effect of anodal/cathodal biphasic electrical stimulation on insulin release.

J Cell Physiol 2019 Feb 11. Epub 2019 Feb 11.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

We studied the effects of electrical stimulation on insulin release from rat insulinoma (INS-1) cells. The anodal/cathodal biphasic stimulation (ACBPS) electrical waveform resulted in a voltage- and stimulation duration-dependent increase in insulin release. ACBPS elicited insulin release both in the presence and absence of glucose. Read More

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http://dx.doi.org/10.1002/jcp.28307DOI Listing
February 2019
3 Reads

Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival.

Cancers (Basel) 2019 Feb 6;11(2). Epub 2019 Feb 6.

Department of Physiology, University of Arizona, Tucson, AZ 85724, USA.

Differential phosphorylation of the carboxyl-terminus of connexin 37 (Cx37-CT) regulates phenotypic switching between cell growth phenotypes (cell death, cell cycle arrest, proliferation). The specific phosphorylation events in the Cx37-CT that are necessary for these growth regulatory effects are currently unknown. Through the combined use of deletion and site specific (de)phospho-mimetic Cx37-CT mutants, our data suggest a phosphorylation-dependent interaction between the mid-tail (aa 273⁻317) and end-tail (aa 318⁻333) portions of the Cx37-CT that regulates cell survival. Read More

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http://dx.doi.org/10.3390/cancers11020188DOI Listing
February 2019
1 Read

Physiopathological premises to Nuclear Medicine Imaging of pancreatic neuroendocrine tumours.

Curr Radiopharm 2019 Feb 5. Epub 2019 Feb 5.

Nuclear Medicine Unit, Department of Clinical and Experimental Medicine ''F.Magrassi, A.Lanzara'' - Università della Campania "Luigi Vanvitelli", Napoli. Italy.

Background: Pancreatic neuroendocrine tumors (P-NETs) are a challenge in terms of both diagnosis and therapy; morphological studies need to be frequently implemented with non standard techniques such as Endoscopic Ultrasounds , Dynamic CT, functional Magnetic Resonance.

Discussion: The role of nuclear medicine's, being scarcely sensitive F-18 Fluorodeoxyglucose, is mainly based on the over-expression of somatostatin receptors (SSTR) on neuroendocrine tumor cells surface. Therefore SSTR can be used as a target for both diagnosis, using radiotracers labeled with gamma or positron emitters, and therapy. Read More

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http://dx.doi.org/10.2174/1874471012666190206094555DOI Listing
February 2019
1 Read

Molecular Imaging to the Surgeons Rescue: Gallium-68 DOTA-Exendin-4 Positron Emission Tomography-Computed Tomography in Pre-operative Localization of Insulinomas.

Indian J Nucl Med 2019 Jan-Mar;34(1):14-18

Department of Paediatric Oncology, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Background: Insulinoma is an islet-cell neoplasm that secretes insulin. It is usually localized to the pancreas and is often the most common cause of endogenous hyperinsulinemic hypoglycaemia in non-diabetic adult patients. Surgical excision with a curative intent is the standard modality of treatment, and it requires precise localization of tumor tissue. Read More

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http://dx.doi.org/10.4103/ijnm.IJNM_119_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352648PMC
February 2019
2 Reads

Negative Effects of Cyclic Palmitate Treatment on Glucose Responsiveness and Insulin Production in Mouse Insulinoma Min6 Cells Are Reversible.

DNA Cell Biol 2019 Jan 31. Epub 2019 Jan 31.

4 Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.

Pancreatic β-cell failure is characterized by compromised insulin secretion in response to glucose, which ultimately results in hyperglycemia, the clinical hallmark of type 2 diabetes mellitus (T2DM). Acute exposure to plasma free fatty acids (FFAs) potentiates glucose stimulated insulin secretion (GSIS), while chronic exposure impairs GSIS, and the latter has been associated with the mechanism of β cell failure in obesity linked T2DM. By contrast, growth hormone (GH) signaling has been linked positively to GSIS in β cells. Read More

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http://dx.doi.org/10.1089/dna.2018.4558DOI Listing
January 2019
1 Read

Prolonged Exposure to Insulin Inactivates Akt and Erk and Increases Pancreatic Islet and INS1E -Cell Apoptosis.

J Endocr Soc 2019 Jan 1;3(1):69-90. Epub 2018 Nov 1.

Division of Clinical and Molecular Endocrinology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio.

Chronic hyperinsulinemia, , increases the resistance of peripheral tissues to insulin by desensitizing insulin signaling. Insulin, in a heterologous manner, can also cause IGF-1 resistance. The aim of the current study was to investigate whether insulin-mediated insulin and IGF-1 resistance develops in pancreatic -cells and whether this resistance results in -cell decompensation. Read More

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http://dx.doi.org/10.1210/js.2018-00140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344346PMC
January 2019

Islet autoantibody positivity in overweight and obese adults with type 2 diabetes.

Autoimmunity 2018 Dec 2;51(8):408-416. Epub 2019 Jan 2.

a Department of Medicine, Division of General Internal Medicine , The Johns Hopkins University School of Medicine, Baltimore , MD , USA.

Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. Read More

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http://dx.doi.org/10.1080/08916934.2018.1547711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362362PMC
December 2018
3 Reads

Viscothionin purified from mistletoe (Viscum album var. coloratum Ohwi) induces insulin secretion from pancreatic beta cells.

J Ethnopharmacol 2019 Apr 17;234:172-179. Epub 2019 Jan 17.

Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.

Ethnopharmacological Relevance: Mistletoe (Viscum album), an evergreen parasitic plant, has been widely used as an oriental phytomedicine to treat diabetes mellitus. However, it is unknown which mistletoe constituent exerts the beneficial effect against the disease. In this study, we examined the hypoglycemic activity of mistletoe and investigated whether the polypeptide viscothionin, purified from mistletoe, was responsible for the activity. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03788741183254
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http://dx.doi.org/10.1016/j.jep.2019.01.014DOI Listing
April 2019
17 Reads

Canine insulinomas appear hyperintense on MRI T2-weighted images and isointense on T1-weighted images.

Vet Radiol Ultrasound 2019 Jan 17. Epub 2019 Jan 17.

Department of Clinical Sciences, Istituto Veterinario di Novara, Novara, 28060, Italy.

Clinical and imaging diagnosis of canine insulinomas has proven difficult due to nonspecific clinical signs and the small size of these tumors. The aim of this retrospective case series study was to describe MRI findings in a group of dogs with pancreatic insulinomas. Included dogs were presented for suspected pancreatic insulinoma, MRI was used to assist with localization of the primary lesion, and the diagnosis was confirmed with surgical exploratory laparotomy and histopathology. Read More

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http://doi.wiley.com/10.1111/vru.12715
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http://dx.doi.org/10.1111/vru.12715DOI Listing
January 2019
7 Reads

Protein Corona Fingerprints of Liposomes: New Opportunities for Targeted Drug Delivery and Early Detection in Pancreatic Cancer.

Pharmaceutics 2019 Jan 15;11(1). Epub 2019 Jan 15.

Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality in the Western world and is envisaged to become the second cause by 2030. Although our knowledge about the molecular biology of PDAC is continuously increasing, this progress has not been translated into better patients' outcome. Liposomes have been used to circumvent concerns associated with the low efficiency of anticancer drugs such as severe side effects and damage of healthy tissues, but they have not resulted in improved efficacy as yet. Read More

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http://dx.doi.org/10.3390/pharmaceutics11010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358751PMC
January 2019
2 Reads

Metastatic Insulinoma Presenting as a Liver Cyst.

J Pathol Transl Med 2019 Jan 16. Epub 2019 Jan 16.

Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.

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http://dx.doi.org/10.4132/jptm.2019.01.15DOI Listing
January 2019
1 Read

Instant evaluation of contrast enhanced endoscopic ultrasound helps to differentiate various solid pancreatic lesions in daily routine.

World J Clin Cases 2019 Jan;7(1):19-27

Department of General Internal Medicine and Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg 21339, Germany.

Background: Contrast enhanced harmonic endoscopic ultrasound (CEH-EUS) is a spreading technique; some studies have shown its value in the diagnosis of pancreatic adenocarcinoma using quantitative analysis.

Aim: To examine the value of CEH-EUS for differentiating various pancreatic lesions in everyday routine with qualitative and quantitative analysis.

Methods: Data of 55 patients with pancreatic lesions who underwent CEH-EUS were analysed retrospectively. Read More

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http://dx.doi.org/10.12998/wjcc.v7.i1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327129PMC
January 2019
2 Reads

Rab8a is involved in membrane trafficking of Kir6.2 in the MIN6 insulinoma cell line.

Pflugers Arch 2019 Jan 10. Epub 2019 Jan 10.

Department of Pharmacology, Faculty of Medicine, Saga University, Saga, 849-8501, Japan.

Although ATP-sensitive K (K) channels play an important role in the secretion of insulin by pancreatic beta cells, the mechanisms that regulate the intracellular transport of K channel subunit proteins (i.e., Kir6. Read More

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http://dx.doi.org/10.1007/s00424-018-02252-1DOI Listing
January 2019
2 Reads

Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children.

Pediatr Diabetes 2019 Jan 10. Epub 2019 Jan 10.

Department of Pediatrics, University of Florida, Gainesville, Florida.

Objective: The capacity to precisely predict progression to type 1 diabetes (T1D) in young children over a short time span is an unmet need. We sought to develop a risk algorithm to predict progression in children with high-risk human leukocyte antigen (HLA) genes followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Methods: Logistic regression and 4-fold cross-validation examined 38 candidate predictors of risk from clinical, immunologic, metabolic, and genetic data. Read More

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http://dx.doi.org/10.1111/pedi.12812DOI Listing
January 2019
2 Reads

Endoplasmic Reticulum Associated Degradation (ERAD) Has a Critical Role in Supporting Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells.

Diabetes 2019 Jan 9. Epub 2019 Jan 9.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cam-Su Genomic Resource Center, Medical College of Soochow University, China 215123

The molecular underpinnings of β-cell dysfunction and death leading to diabetes are not fully elucidated. The objective of the present study was to investigate the role of endoplasmic reticulum associated degradation (ERAD) in pancreatic β-cells. Chemically induced ERAD deficiency in the rat insulinoma cell line INS-1 markedly reduced glucose-stimulated insulin secretion (GSIS). Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db18
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http://dx.doi.org/10.2337/db18-0624DOI Listing
January 2019
11 Reads

Early F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma.

Eur J Nucl Med Mol Imaging 2019 03 7;46(3):686-695. Epub 2019 Jan 7.

Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, Strasbourg, France.

Purpose: Data on the diagnostic value of F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated. Read More

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http://dx.doi.org/10.1007/s00259-018-4245-3DOI Listing
March 2019
3 Reads

Vitronectin, fibronectin and epidermal growth factor induce proliferation via the JNK and ERK pathways in insulinoma INS-1 cells.

Cytotechnology 2019 Feb 2;71(1):209-217. Epub 2019 Jan 2.

Department of Biology, Faculty of Science, Istanbul University, Vezneciler, 34134, Istanbul, Turkey.

An insulinoma is a tumor formed by beta cells in the Langerhans islets of the pancreas. Vitronectin (VTN), fibronectin (FN) and epidermal growth factor (EGF) are important in cell signaling. The aim of this study was to investigate the molecular mechanism that occurs in INS-1 cells with the administration of VTN, FN and EGF in proliferative doses. Read More

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http://dx.doi.org/10.1007/s10616-018-0277-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368526PMC
February 2019
1 Read

A case of hyperinsulinemic hypoglycemia related with a calcimimetic agent.

Diabetol Int 2018 Jul 21;9(3):196-200. Epub 2018 Feb 21.

Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543 Japan.

We herein report a case of a 60-year-old female receiving hemodialysis who developed severe hyperinsulinemic hypoglycemia and lost her consciousness. A calcimimetic agent had been administered for the secondary hyperparathyroidism. The calcimimetic agent, mimicking the elevation of the extracellular calcium ion concentration, activates calcium-sensing receptors (CaSR) of the parathyroid cells and inhibits the parathyroid hormone secretions. Read More

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http://dx.doi.org/10.1007/s13340-018-0350-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224912PMC
July 2018
2 Reads

A Case Report of Insulinoma Relapse on Background Nesidioblastosis: A Rare Cause of Adult Hypoglycemia.

J Clin Endocrinol Metab 2019 Mar;104(3):773-778

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.

Context: Nesidioblastosis is a rare cause of adult hypoglycemia. Current medical therapy can mitigate disease symptoms. However, side effects and limited efficacy may prevent long-term disease management. Read More

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http://dx.doi.org/10.1210/jc.2018-02007DOI Listing
March 2019
4 Reads

A case of malignant insulinoma responsive to somatostatin analogs treatment.

BMC Endocr Disord 2018 Dec 27;18(1):98. Epub 2018 Dec 27.

Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Careggi University Hospital, Florence, Italy.

Background: Insulinoma is a rare tumour representing 1-2% of all pancreatic neoplasms and it is malignant in only 10% of cases. Locoregional invasion or metastases define malignancy, whereas the dimension (> 2 cm), CK19 status, the tumor staging and grading (Ki67 > 2%), and the age of onset (> 50 years) can be considered elements of suspect.

Case Presentation: We describe the case of a 68-year-old man presenting symptoms compatible with hypoglycemia. Read More

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http://dx.doi.org/10.1186/s12902-018-0325-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307122PMC
December 2018
2 Reads

Creation of versatile cloning platforms for transgene expression and dCas9-based epigenome editing.

Nucleic Acids Res 2019 Feb;47(4):e23

Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA.

Genetic manipulation via transgene overexpression, RNAi, or Cas9-based methods is central to biomedical research. Unfortunately, use of these tools is often limited by vector options. We have created a modular platform (pMVP) that allows a gene of interest to be studied in the context of an array of promoters, epitope tags, conditional expression modalities, and fluorescent reporters, packaged in 35 custom destination vectors, including adenovirus, lentivirus, PiggyBac transposon, and Sleeping Beauty transposon, in aggregate >108,000 vector permutations. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gky1286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393299PMC
February 2019
10 Reads

Mitochondrial lysine deacetylation promotes energy metabolism and calcium signaling in insulin-secreting cells.

FASEB J 2018 Dec 27:fj201801424R. Epub 2018 Dec 27.

Mitochondrial Function, Nestlé Institute of Health Sciences, Lausanne, Switzerland.

In pancreatic β-cells, mitochondria generate signals that promote insulin granule exocytosis. Here we study how lysine acetylation of mitochondrial proteins mechanistically affects metabolism-secretion coupling in insulin-secreting cells. Using mass spectrometry-based proteomics, we identified lysine acetylation sites in rat insulinoma cell line clone 1E cells. Read More

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http://dx.doi.org/10.1096/fj.201801424RDOI Listing
December 2018
1 Read

Evaluation of cellular and humoral autoimmunity before the development of type 1 diabetes in a patient with idiopathic CD4 lymphocytopenia.

J Diabetes Investig 2018 Dec 26. Epub 2018 Dec 26.

Department of Diabetes, Endocrinology and Metabolism, Tokyo, Japan.

A 64-year-old woman developed type 1 diabetes 23 years after the diagnosis of idiopathic CD4 lymphocytopenia. To investigate the etiological interaction between idiopathic CD4 lymphocytopenia and type 1 diabetes, we carried out a longitudinal analysis related to islet-specific autoimmunity. Anti-glutamic acid decarboxylase antibody had been already weakly positive for at least 16 years and started rising at 6 months before the onset of type 1 diabetes. Read More

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http://dx.doi.org/10.1111/jdi.12997DOI Listing
December 2018
2 Reads

Cellular toxicity of dietary trans fatty acids and its correlation with ceramide and diglyceride accumulation.

Food Chem Toxicol 2019 Feb 17;124:324-335. Epub 2018 Dec 17.

Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Budapest, Hungary. Electronic address:

High fatty acid (FA) levels are deleterious to pancreatic β-cells, largely due to the accumulation of biosynthetic lipid intermediates, such as ceramides and diglycerides, which induce ER stress and apoptosis. Toxicity of palmitate (16:0) and oleate (18:1 cis-Δ) has been widely investigated, while very little data is available on the cell damages caused by elaidate (18:1 trans-Δ) and vaccenate (18:1 trans-Δ), although the potential health effects of these dietary trans fatty acids (TFAs) received great publicity. We compared the effects of these four FAs on cell viability, apoptosis, ER stress, JNK phosphorylation and autophagy as well as on ceramide and diglyceride contents in RINm5F insulinoma cells. Read More

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http://dx.doi.org/10.1016/j.fct.2018.12.022DOI Listing
February 2019
1 Read

Symptomatic and Radiological Response to 177Lu-DOTATATE for the Treatment of Functioning Pancreatic Neuroendocrine Tumors.

J Clin Endocrinol Metab 2019 Apr;104(4):1336-1344

Department of Internal Medicine, Sector of Endocrinology, Erasmus Medical Center and Erasmus MC Cancer Institute, Rotterdam, Netherlands.

Purpose: Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs.

Methods: Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7. Read More

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http://dx.doi.org/10.1210/jc.2018-01991DOI Listing
April 2019
8 Reads

Evaluating the utility of human glucagon-like peptide 1 receptor gene as a novel radionuclide reporter gene: a promising molecular imaging tool.

Appl Microbiol Biotechnol 2019 Feb 18;103(3):1311-1324. Epub 2018 Dec 18.

Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.

Radiolabelled ligands of glucagon-like peptide 1 receptor (GLP-1R) have been used to image the GLP-1R-expressing tissues (e.g., islets and insulinoma). Read More

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http://dx.doi.org/10.1007/s00253-018-9562-8DOI Listing
February 2019
1 Read

Apatinib inhibits tumor growth and angiogenesis in PNET models.

Endocr Connect 2019 Jan;8(1):8-19

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Angiogenesis has a pivotal role in the growth and metastasis of pancreatic neuroendocrine tumors (PNETs). Apatinib inhibits angiogenesis as a highly selective KDR inhibitor and has been used to treat advanced gastric cancer and malignancies in clinical settings. However, the efficacy of apatinib in PNETs remains unclear. Read More

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http://dx.doi.org/10.1530/EC-18-0397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330719PMC
January 2019
17 Reads

Expression of Insulinoma-Associated Protein 1 (INSM1) and Orthopedia Homeobox (OTP) in Tumors with Neuroendocrine Differentiation at Rare Sites.

Endocr Pathol 2019 Mar;30(1):35-42

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Insulinoma-associated protein 1 (INSM1) and orthopedia homeobox (OTP) are transcription factors that play a critical role in neuroendocrine (NE) and neuroepithelial cell development. INSM1 has been identified in multiple tumors of NE or neuroepithelial origin, whereas OTP expression has been mainly studied in NE tumors of pulmonary origin. Expression of OTP appears to correlate with poorer prognosis in pulmonary carcinoids; however, its expression patterns in other NE/neuroepithelial tumors need further investigation. Read More

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http://dx.doi.org/10.1007/s12022-018-9559-yDOI Listing
March 2019
2 Reads

Clinical Management of Malignant Insulinoma: a single Institution's experience over three decades.

BMC Endocr Disord 2018 Dec 6;18(1):92. Epub 2018 Dec 6.

Department of Endocrinology, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China.

Background: Malignant insulinoma is extremely rare and accounts for only 10% of total insulinoma cases. The goal of this study is to retrospectively analyze clinical data from 15 patients with malignant insulinoma treated at Peking Union Medical College Hospital (PUMCH) from 1984 to April 2017.

Methods: "Malignant insulinoma" was used as the keywords in the PUMCH medical record retrieval system to search and obtain patients' clinical information. Read More

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http://dx.doi.org/10.1186/s12902-018-0321-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282250PMC
December 2018
3 Reads

Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells.

Cell Physiol Biochem 2018 7;51(5):2185-2197. Epub 2018 Dec 7.

Department of Medicine, The University of Chicago, Chicago, Illinois,

Background/aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in β-cells, however, the role of VIMP in β-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and β-cell survival in MIN6 insulinoma cells.

Methods: To determine the role of VIMP in β-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Read More

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https://www.karger.com/Article/FullText/495865
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http://dx.doi.org/10.1159/000495865DOI Listing
January 2019
2 Reads

Characterization of Transplantable Insulinoma Cells.

Authors:
Paul C Guest

Methods Mol Biol 2019 ;1916:213-222

Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.

This chapter describes the propagation and characterization of transplantable insulinoma cells as model of insulin-producing pancreatic islet cells in the rat. Here, the cells are propagated by transplantation into rats followed by harvesting after growth for approximately 1 month. The cells are then purified by Percoll density gradient centrifugation and characterized by pulse-chase radiolabelling and immunoprecipitation of the insulin-related peptides. Read More

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http://dx.doi.org/10.1007/978-1-4939-8994-2_20DOI Listing
January 2019

Autoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients.

Endocrinol Diabetes Metab Case Rep 2018 Dec 11;2018. Epub 2018 Dec 11.

ENETS Center of Excellence, Department of Medicine, University of Verona, Verona, Italy.

Insulin autoimmune syndrome (IAS), a rare cause of autoimmune hyperinsulinaemic hypoglycaemia, is relatively well known in Japan. The incidence in Caucasians is less than one-fifth of that reported in Japanese people, but it is becoming increasingly recognised worldwide in non-Asians as well. Drugs containing sulphydryl groups are known to be associated with the disease in genetically predisposed individuals. Read More

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https://edm.bioscientifica.com/view/journals/edm/2018/1/EDM1
Publisher Site
http://dx.doi.org/10.1530/EDM-18-0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300856PMC
December 2018
3 Reads

Spontaneously remitting insulin autoimmune syndrome in a patient taking alpha-lipoic acid.

Endocrinol Diabetes Metab Case Rep 2018 Dec 11;2018. Epub 2018 Dec 11.

Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare hypoglycaemic disorder caused by the presence of high titer of insulin autoantibodies (IAA) in patients without previous exposure to exogenous insulin. Even though its pathogenesis is not fully understood, striking evidences link IAS to previous exposure to sulphydryl-containing medications, like alpha-lipoic acid, a widely used nutritional supplement. Although challenging, a careful differential diagnosis from other causes of hyperinsulinaemic hypoglycaemia (such as insulinoma) is mandatory, since these conditions require different therapeutic approaches. Read More

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https://edm.bioscientifica.com/view/journals/edm/2018/1/EDM1
Publisher Site
http://dx.doi.org/10.1530/EDM-18-0122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300855PMC
December 2018
18 Reads

Clinical outcomes of 20 Japanese patients with insulinoma treated with diazoxide.

Endocr J 2019 Feb 30;66(2):149-155. Epub 2018 Nov 30.

Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.

Diazoxide is recognized as an effective medical treatment for insulinoma. However, due to its adverse effects, such as fluid retention, it is sometimes difficult to employ diazoxide at an effective dose in clinical practice. This study aimed to clarify the clinical factors, which may affect efficacy and safety of the diazoxide treatment. Read More

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https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub
Publisher Site
http://dx.doi.org/10.1507/endocrj.EJ18-0353DOI Listing
February 2019
11 Reads