Pancreatic Cell News Volume 6.25 | Jun 30 2015

Cytokines Induce Endoplasmic Reticulum Stress in Human, Rat and Mouse Beta Cells via Different Mechanisms
Scientists explored the role of endoplasmic reticulum stress on cytokine-induced beta cell apoptosis in three species and thus solved ongoing controversies in the field. Rat and mouse insulin-producing cells, human pancreatic islets and human EndoC-βH1 cells were exposed to the cytokines IL-1β, TNF-α and IFN-γ, with or without NO inhibition. [Diabetologia] Abstract

Pancreatic Alpha-Cells from Female Mice Undergo Morphofunctional Changes during Compensatory Adaptations of the Endocrine Pancreas to Diet-Induced Obesity
Investigators studied alpha-cells in mice fed a high-fat diet for twelve weeks. In vitro glucagon release at low glucose levels and glucagon content in isolated islets were decreased, while alpha-cell exocytosis remained unchanged. [Sci Rep] Full Article

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic Beta- and Alpha-Cells
One novel microRNA, miR-483 was identified for its highly differential expression in pancreatic β-cells but much less in α-cells. Overexpressed miR-483 protected against proinflammatory cytokine-induced apoptosis in β-cells. [J Biol Chem] Abstract | Full Article

GPR39 Receptors and Actions of Trace Metals on Pancreatic Beta Cell Function and Glucose Homoeostasis
Researchers used clonal BRIN-BD11 cells and mouse pancreatic islets to assess the insulin-releasing actions of trace metals believed to act via GPR39, and the second messenger pathways involved in mediating their effects. [Acta Diabetol] Abstract

The Effect of Nrf2 Pathway Activation on Human Pancreatic Islet Cells
The authors investigated the effect of Nrf2 activator (dh404, CDDO-9,11-dihydro-trifluoroethyl amide) on human islet cells. The cytoprotective effects against oxidative stress and production of inflammatory mediators, and in vivo islet function after transplantation were determined. [PLoS One] Full Article

PANCREATIC CANCER

Zidovudine, an Anti-Viral Drug, Resensitizes Gemcitabine-Resistant Pancreatic Cancer Cells to Gemcitabine by Inhibition of the Akt-GSK3β-Snail Pathway
Researchers demonstrated that co-administration of zidovudine and gemcitabine strongly suppressed the formation of tumors by gemcitabine-resistant pancreatic cancer and prevented gemcitabine-sensitive pancreatic tumors from acquiring gemcitabine-resistant properties, inducing an epithelial-to-mesenchymal transition-like phenotype and downregulating human equilibrative nucleoside transporter 1 expression. [Cell Death Dis] Full Article

Pyruvate Kinase Isoenzyme M2 Is a Therapeutic Target of Gemcitabine-Resistant Pancreatic Cancer Cells
Investigators identified molecular features involved in gemcitabine chemoresistance. They report that the chemoresistance of pancreatic cancer to gemcitabine was dependent on pyruvate kinase M2 expression and its non-metabolic function. [Exp Cell Res] Abstract

miR-33a Suppresses the Nuclear Translocation of β-Catenin to Enhance Gemcitabine Sensitivity in Human Pancreatic Cancer Cells
Scientists observed that miR-33a targeted the 3′UTR of β-catenin, inducing apoptosis and inhibiting the growth of human pancreatic cancer cells. Gemcitabine treatment enhanced β-catenin expression by reducing miR-33a expression in a dose-dependent manner. [Tumor Biol] Abstract

Quercetin 3-O-Glucoside Suppresses Epidermal Growth Factor-Induced Migration by Inhibiting EGFR Signaling in Pancreatic Cancer Cells
Investigators examined the anti-migratory effect of quercetin 3-O-glucoside in epidermal growth factor (EGF)-induced cell migration by inhibiting EGF receptor (EGFR) signaling in several human pancreatic cancer cell lines. [Tumor Biol] Abstract

Decoy Receptor 3 Suppresses FasL-Induced Apoptosis via ERK1/2 Activation in Pancreatic Cancer Cells
Researchers investigated the role of decoy receptor 3 in resistance to Fas ligand (FasL) in pancreatic cancer. They compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. [Biochem Biophys Res Commun] Abstract

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Vitae Pharmaceuticals Announces Top-Line Results from Metformin Arm of Ongoing Phase II Clinical Trial of BI187004/VTP-34072 in Overweight Type 2 Diabetics
Vitae Pharmaceuticals, Inc. announced top-line clinical efficacy results from the metformin arm of an ongoing Phase II proof-of-concept clinical trial of BI187004/VTP-34072 in the treatment of overweight type 2 diabetic patients. [Vitae Pharmaceuticals, Inc.] Press Release

Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-κB Ligand Pathway
PharmaCyte Biotech will partner with the University of Technology Sydney to co-develop the company’s preclinical treatment for insulin-dependent diabetes that uses its Cell-in-a-Box® technology. [PharmaCyte Biotech] Press Release

Services and Research Collaboration Agreement between CellResearch Corporation Pte Ltd and the University of Colorado School of Medicine
The Board of Directors of CellResearch Corporation Pte Ltd (CRC) announced that it has entered into a Services and Research Collaboration Agreement with the University of Colorado School Of Medicine and ClinImmune Labs. This first collaboration will focus on the development of CRC’s proprietary and patented Cord Lining Mesenchymal Stem Cells for the Treatment of Diabetic Wounds. [CellResearch Corporation Pte Ltd] Press Release

Scripps Florida Scientists Awarded $3.5 Million to Expand Development of New Diabetes Therapies
Scientists from the Florida campus of The Scripps Research Institute have been awarded $3.5 million from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health to accelerate development of a new class of anti-diabetic compounds. [The Scripps Research Institute] Press Release

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NEW Postdoctoral Fellowship – Immunopathogenesis of Type 1 Diabetes (Tongji Medical College)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

PhD Student – Diabetes (Danish Diabetes Academy)

Research Associate – Cancer Therapeutics (University of Cambridge)

Postdoctoral Position – Adipocyte Development (German Institute of Human Nutrition)

Postdoctoral Research Associate – Type 1 Diabetes and Other Autoimmune Diseases (Benaroya Research Institute at Virginia Mason)

PhD Position – Pancreatic Diseases (University Hospital Zurich)

Postdoctoral Position – Metabolic Fingerprinting of Gestational Diabetes Mellitus (CEU San Pablo University)

Postdoctoral Position – Cancer (MD Anderson Cancer Center)

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