DIABETES & PANCREATITIS 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 |