Pancreatic Cell News Volume 7.19 | May 17 2016

Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes
Researchers demonstrated increased melatonin receptor 1 b gene (MTNR1B) expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing type 2 diabetes risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. [Cell Metab]
Full Article | Graphical Abstract | Press Release 

Potentiation of Glucose-Stimulated Insulin Secretion by the GPR40–PLC–TRPC Pathway in Pancreatic β-Cells
Investigators demonstrated that glucagon-like peptide 1, a ligand of pancreatic G protein-coupled receptor (GPCR), activates a class of nonselective cation channels (NSCCs) and enhances glucose-stimulated insulin secretion. The aim of the current study was to determine whether the GPR40 signal interacts with NSCCs. [Sci Rep] Full Article

Extracellular Acidification Stimulates GPR68 Mediated IL-8 Production in Human Pancreatic β Cells
Using the recently developed human β-cell line EndoC-βH2, the authors demonstrated that β-cells respond to extracellular acidification through GPR68, which is the predominant proton sensing receptor of human β-cells. [Sci Rep] Full Article

Reprogramming of Pancreatic Exocrine Cells AR42J Into Insulin-Producing Cells Using mRNAs for Pdx1, Ngn3, and MafA Transcription Factors
With the aim of developing a nonintegrative reprogramming strategy for derivation of insulin-producing cells, scientists evaluated a new approach utilizing synthetic messenger RNAs encoding reprogramming transcription factors. [Mol Ther Nucleic Acids] Full Article

PANCREATIC CANCER

SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b
The authors uncovered an epigenetic program mediated by the NAD⁺-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma, one of the most lethal malignancies. [Cell] Abstract | Graphical Abstract

Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression
Scientists report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates anti-tumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of pancreatic ductal adenocarcinoma. [Cancer Discov] Abstract | Full Article

Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment
Investigators aimed to identify novel epigenetic regulators contributing to the biology of pancreatic ductal adenocarcinoma. [Clin Cancer Res] Abstract

Anti-Metastatic Potential of Somatostatin Analog SOM230: Indirect Pharmacological Targeting of Pancreatic Cancer-Associated Fibroblasts
Using primary cultures of cancer-associated fibroblasts (CAFs) isolated from human pancreatic ductal adenocarcinoma resections, the authors report that CAF secretome stimulates in vitro cancer cell survival, migration and invasive features, that are abolished when CAFs are treated with the somatostatin analog SOM230 (pasireotide). [Oncotarget] Full Article

Antibody-Mediated Neutralization of Autocrine Gas6 Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Tumors In Vivo
A strategy was devised to generate fully human neutralizing antibodies against Gas6 using XenoMouse^® technology. Hybridoma supernatants were selected based on their ability to inhibit Gas6 binding to the receptor Axl and block Gas6-induced Axl phosphorylation in human cells. [Int J Cancer] Abstract

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Large Clinical Study Demonstrates High Detection Rate and Ability to Monitor KRAS Mutations in Pancreatic Cancer Patients
Trovagene, Inc. announced that clinical study results featuring the company’s Precision Cancer Monitoring^® (PCM) platform were presented. The poster, entitled Detection and Quantification of ctDNA KRAS Mutations from Patients with Unresectable Pancreatic Cancer, was presented by Fernando Blanco, Ph.D., medical science liaison at Trovagene. [Press release from Trovagene, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Special Conference on Pancreatic Cancer, Orlando] Press Release

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Aduro Biotech Announces Phase IIb ECLIPSE Trial Misses Primary Endpoint in Heavily Pretreated Metastatic Pancreatic Cancer
Aduro Biotech, Inc. announced that the Phase IIb ECLIPSE trial did not meet the primary endpoint of an improvement in overall survival for patients with pancreatic cancer who had failed at least two prior therapies in the metastatic setting. [Aduro Biotech, Inc.] Press Release

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Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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NEW Postdoctoral Fellow – Diabetes Mellitus and Metabolic Syndrome (Northwestern University)

NEW Associate Senior Lecturer – Medical Cell Biology or Physiology (Uppsala University)

Postdoctoral Fellow – Type 2 Diabetes and Insulin Resistance (King Abdullah University of Science and Technology)

PhD Studentship – Type 2 Diabetes and Insulin Resistance (King Abdullah University of Science and Technology)

Postdoctoral Fellow(s) – Pancreatic Islet Biology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Somatic Stem Cell Biology of Liver/Pancreas (The Swiss Federal Institute of Technology in Zurich)

Postdoctoral Fellow – Pancreas Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Diabetic Peripheral Neuropathy (University of North Dakota)

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

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