Pancreatic Cell News Volume 7.11 | Mar 22 2016

Genetic Predisposition for Beta Cell Fragility Underlies Type 1 and Type 2 Diabetes
Investigators found a new genetic component of diabetes susceptibility in type 1 diabetes non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 altered the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. [Nat Genet] Abstract | Press Release

Functional Identification of a Neurocircuit Regulating Blood Glucose
Scientists report that selective inhibition of the subset of hypothalamic ventromedial nucleus (VMN) neurons that express the transcription factor steroidogenic-factor 1 (VMN^SF1 neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMN^SF1 neurons causes diabetes-range hyperglycemia. [Proc Natl Acad Sci USA] Abstract

α/β-Hydrolase Domain 6 Deletion Induces Adipose Browning and Prevents Obesity and Type 2 Diabetes
The authors report that high-fat-diet-fed α/β-domain hydrolase-6-KO mice show modestly reduced food intake, decreased body weight gain and glycemia, improved glucose tolerance and insulin sensitivity, and enhanced locomotor activity. [Cell Rep] Full Article | Graphical Abstract

Rapid Elevation in CMPF May Act as a Tipping Point in Diabetes Development
To evaluate the effect of increasing CMPF on diabetes progression, researchers used obese, insulin-resistant models of prediabetes. CMPF accelerated diabetes development by inducing metabolic remodeling, resulting in preferential utilization of fatty acids over glucose. [Cell Rep] Full Article | Graphical Abstract

Glucagon-Like Peptide-1 Prevents Methylglyoxal-Induced Apoptosis of Beta Cells through Improving Mitochondrial Function and Suppressing Prolonged AMPK Activation
Researchers explored the signaling pathway involved in the anti-apoptotic effect of GLP-1, and investigated whether metformin had an anti-apoptotic effect on beta cells. [Sci Rep] Full Article

Ursodeoxycholic Acid and 4-Phenylbutyrate Prevent Endoplasmic Reticulum Stress-Induced Podocyte Apoptosis in Diabetic Nephropathy
The authors investigated the role of endoplasmic reticulum stress inhibitors ursodeoxycholic acid and 4-phenylbutyrate in the treatment of diabetic nephropathy in db/db mice. [Lab Invest] Abstract

PANCREATIC CANCER

Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma (PDAC)-Specific RNA Aptamers Inhibits Tumor Growth In Vivo
Scientists report a novel method for delivery of anti-tumorigenic therapy in PDAC by up-regulating the transcriptional factor CCAAT/enhancer-binding protein-a (C/EBPα), recognized for its antiproliferative effects. [Mol Ther] Full Article

Molecular Network, Pathway, and Functional Analysis of Time-Dependent Gene Changes Associated with Pancreatic Cancer Susceptibility to Oncolytic Vaccinia Virotherapy
Researchers determined changes in gene expression patterns associated with infection and susceptibility of pancreatic cancer cells to an oncolyticvaccinia virus, GLV-1h153, carrying the human sodium iodide symporter for deep tissue imaging of virotherapy. [Mol Ther Oncolytics] Full Article

Assessment of Bone Turnover and Bone Quality in Type 2 Diabetic Bone Disease: Current Concepts and Future Directions
Bone imaging technologies, including trabecular bone score and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. [Bone Res] Full Article

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Real-World Data on XARELTO^® in Patients with Non-Valvular Atrial Fibrillation and Diabetes Among 13 Presentations at American College of Cardiology’s 65th Annual Scientific Session
Janssen Pharmaceuticals Inc. and Bayer announced that 13 data presentations will be presented including real-world findings confirming the safety of XARELTO^® (rivaroxaban) in a high-risk group of patients with non-valvular atrial fibrillation and concomitant diabetes. [Press release from Janssen Pharmaceuticals, Inc. discussing research to be presented at the American College of Cardiology’s 65th Annual Scientific Session (ACC.16), Chicago] Press Release

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Targovax Announces Encouraging Interim Results with Ras Specific Pepetide Vaccine in Resected Pancreatic Cancer
Targovax has conducted a predetermined interim analysis of the TG01 Phase I/II trial, indicating promising one year overall survival data when combining TG01 with gemcitabine (chemotherapy) as supplementary treatment of patients with pancreatic cancer. [Targovax] Press Release

MabVax Therapeutics Initiates Phase I Trial of HuMab-5B1 for Treatment of Pancreatic Cancer
MabVax Therapeutics Holdings, Inc. announced initiation of a Phase I clinical trial of HuMab-5B1 for patients with locally advanced or metastatic adenocarcinoma of the pancreas or other CA19-9 positive malignancies. [MabVax Therapeutics Holdings, Inc.] Press Release

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Postdoctoral Fellowship – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

Master Studentship – Exercise and Diabetes (Swansea University)

Part Time Researcher – Diabetes (University of Bergen)

Postdoctoral Research Fellowship – Pancreatic Cancer Biology (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellowship – Surgical Oncology in Pancreatic Cancer (University of Nebraska Medical Center)

Postdoctoral Research Fellowship – Pancreatic Progenitors in Development (Johns Hopkins University Institute of Genetic Medicine)

Postdoctoral Fellowship – Metabolism and Cancer (Monash University)

Postdoctoral Fellowship – Mechanisms of Atherosclerosis, Diabetes and Obesity (Washington University School of Medicine)

Assistant Professor of Surgery – Molecular Biology and Pancreatic Development (University of Pittsburgh)

Postdoctoral Fellowship – Neural Mechanisms of Diabetes (Albert Einstein College of Medicine)

Faculty Position – Metabolic Disease Research (Lewis Katz School of Medicine)

Post-Doc Fellowship – Glucose Metabolism (Joslin Diabetes Center)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

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