Pancreatic Cell News Volume 7.14 | Apr 12 2016

ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells
Researchers identified estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal β cells. Postnatal induction of ERRγ drove a transcriptional network activating mitochondrial oxidative phosphorylation, the electron transport chain, and ATP production needed to drive glucose-responsive insulin secretion. [Cell Metab] Full Article | Graphical Abstract | Press Release 

Stress-Impaired Transcription Factor Expression and Insulin Secretion in Transplanted Human Islets
The authors examined the mechanistic consequences of glucotoxic and lipotoxic conditions on human islets in vivo and developed and/or used three complementary models that allowed comparison of the effects of hyperglycemic and/or insulin-resistant metabolic stress conditions on human and mouse islets, which responded quite differently to these challenges. [J Clin Invest] Full Article

A Programmable Synthetic Lineage-Control Network that Differentiates Human iPSCs into Glucose-Sensitive Insulin-Secreting Beta-Like Cells
A designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3 (neurogenin 3), Pdx1 (pancreatic and duodenal homeobox 1) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A) variants was able to program human induced pluripotent stem cells (iPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics were comparable to human pancreatic islets. [Nat Commun] Full Article | Press Release

Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation
The authors investigated the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic mouse model. [Cell Rep] Full Article | Graphical Abstract

Interleukin-1 Signaling Contributes to Acute Islet Compensation
Scientists found that the ability of interleukin (IL)-1β to amplify glucose-stimulated insulin secretion from human islets correlates with donor BMI. Islets from obese donors were sensitized to the insulinotropic effects of this cytokine, whereas the stimulatory effects of IL-1β were lost in islets from obese type 2 diabetic patients, suggesting a role for IL-1 signaling in islet compensation. [JCI Insight] Full Article | Press Release

PANCREATIC CANCER

Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis
Investigators showed that doublecortin-like kinase-1 (Dclk1) labels a rare population of long-lived, quiescent pancreatic cells. In vitro, Dclk1⁺ cells proliferated readily and sustained pancreatic organoid growth. In vivo, Dclk1⁺ cells were necessary for pancreatic regeneration following injury and chronic inflammation. [Cell Stem Cell] Full Article | Graphical Abstract

Downregulated miR-506 Expression Facilitates Pancreatic Cancer Progression and Chemoresistance via SPHK1/Akt/NF-κB Signaling
Scientists discovered a novel epigenetic mechanism of miR-506 regulation and investigated its functional significance in pancreatic cancer. [Oncogene] Full Article

Anti-Stromal Treatment Together with Chemotherapy Targets Multiple Signaling Pathways in Pancreatic Adenocarcinoma
Gemcitabine and all-trans retinoic acid were combined in a clinically applicable regimen, to target cancer cells and pancreatic stellate cells respectively, in 3D organotypic culture models and genetically engineered mice representing the spectrum of pancreatic ductal adenocarcinoma. [J Pathol] Abstract

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Kadimastem Is Granted a Patent in Japan for Diabetes Treatment
Kadimastem announced it was granted a patent from the Japanese Patent Office for its technology in the field of diabetes treatment. The patent is for a method of producing insulin-secreting cells from stem cells, and it is likely to constitute the foundation for the company’s products in the field of stem-cell based treatment of diabetes. [Kadimastem] Press Release

Oramed Receives Patent Term Adjustment Extending the Term of Its U.S. Patent
Oramed Pharmaceuticals Inc. announced that the U.S. Patent and Trademark Office has issued a Patent Term Adjustment extending the patent term by 18 months for its patent, “Methods and Compositions for Oral Administration of Proteins.” The patent addresses Oramed’s platform technology which underlies its products, including ORMD-0801, an orally ingestible insulin capsule. [Oramed Pharmaceuticals Inc. (PR Newswire Association LLC.)] Press Release

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Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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NEW Postdoctoral Fellowship – Diabetes and Metabolic Disorder (Pere Virgili Health Research Institute)

Group Leader – Stem Cell Biology, Pancreatic Cancer and Bioengineering (University of Copenhagen)

PhD Studentship – Regulation of Metabolism (University of Wuerzburg)

Postdoctoral Fellow – Diabetes Induced Neural Tube Defects (UMB School of Medicine)

Postdoctoral Fellow – Pancrease Preconditioning (Centre Européen d’Etude du Diabète)

Postdoctoral Fellow – Pancreatic Zinc Transporter as Therapeutic Target (Johns Hopkins School of Medicine)

Research Scientist – Various Fields (King Abdullah International Medical Research Center)

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

Master Studentship – Exercise and Diabetes (Swansea University)

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)

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