DIABETES & PANCREATITIS Metformin Activates Duodenal AMPK and a Neuronal Network to Lower Glucose Production Researchers showed that intraduodenal infusion of metformin for 50 min activated duodenal mucosal AMP-activated protein kinase (AMPK) and lowered hepatic glucose production in a rat three day high fat diet-induced model of insulin resistance. [Nat Med] Abstract | Press Release Epigenetic Priming of Enhancers Predicts Developmental Competence of hESC-Derived Endodermal Lineage Intermediates Investigators report that epigenetic priming of enhancers signifies developmental competence during endodermal lineage diversification. Chromatin mapping during pancreatic and hepatic differentiation of human embryonic stem cells revealed the en masse acquisition of a poised chromatin state at enhancers specific to endoderm-derived cell lineages in gut tube intermediates. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release Insm1 Cooperates with Neurod1 and Foxa2 to Maintain Mature Pancreatic β-Cell Function The authors showed that Insm1, Neurod1 and Foxa2 directly interacted and together bind regulatory sequences in the genome of mature pancreatic β-cells. They used Insm1 ablation in mature β-cells in mice and found pronounced deficits in insulin secretion and gene expression. [EMBO J] Full Article | Graphical Abstract Glucose Tolerance Is Improved in Mice Invalidated for the Nuclear Receptor HNF-4 Gamma: A Critical Role for Enteroendocrine Cell Lineage GLP-1 exerted a trophic effect on pancreatic β-cells and researchers report an increase of the β-cell fraction correlated with an augmented number of proliferative islet cells and with resistance to streptozotocin-induced diabetes. [Diabetes] Abstract Inducible VEGF Expression by Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Reduces the Minimal Islet Mass Required to Reverse Diabetes Scientists hypothesized that co-transplantation of islets with human embryonic stem cell-derived mesenchymal stromal cells that conditionally overexpress VEGF may augment islet revascularization and reduce the minimal islet mass required to reverse diabetes in mice. [Sci Rep] Full Article Redox Signal-Mediated Enhancement of the Temperature Sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) Elevated Glucose-Induced Insulin Secretion from Pancreatic Islets Researchers focused on the physiological functions of redox signal-mediated transient receptor potential melastatin 2 (TRPM2) activity at body temperature. H2O2, an important molecule in redox signaling, reduced the temperature threshold for TRPM2 activation in pancreatic β-cells of wild-type mice, but not in TRPM2KO cells. [J Biol Chem] Abstract | Full Article PANCREATIC CANCER Microenvironmental hCAP-18/LL-37 Promotes Pancreatic Ductal Adenocarcinoma by Activating Its Cancer Stem Cell Compartment Treatment of pancreatic cancer stem cells with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumorigenicity via formyl peptide receptor 2- and P2X purinoceptor 7 receptor-dependent mechanisms, which could be reversed by inhibiting these receptors. [Gut] Abstract Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer Researchers report for the first time that a nonsteroidal drug, ormeloxifene (ORM), has potent anti-cancer properties and depletes tumor-associated stromal tissue by inhibiting the sonic hedgehog signaling pathway in pancreatic ductal adenocarcinoma (PDAC). They found that ORM inhibited cell proliferation and induced death in PDAC cells, which provoked them to investigate the combinatorial effects of ORM with gemcitabine at the molecular level. [Cancer Res] Abstract Omeprazole Inhibits Pancreatic Cancer Cell Invasion through a Non-Genomic Aryl Hydrocarbon Receptor Pathway Treatment of highly invasive Panc1 pancreatic cancer cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole and seven other AhR-active pharmaceuticals showed that only omeprazole and tranilast but not TCDD inhibited invasion in a Boyden chamber assay. [Chem Res Toxicol] Abstract Effects of Ropivacaine, Bupivacaine and Sufentanil in Colon and Pancreatic Cancer Cells In Vitro Scientists investigated the effects of the clinically used local anesthetics ropivacaine or bupivacaine and the opioid analgesic sufentanil on cell proliferation, cell cycle distribution and apoptosis of colon and pancreatic cancer cell lines in vitro. [Pharmacol Res] Abstract Superoxide Dismutase Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells via Activation of the H2O2/ERK/NF-κB Axis Scientists evaluated whether superoxide dismutase (SOD) affects epithelial-mesenchymal transition in pancreatic cancer cells and the related mechanism. Human pancreatic cancer cells BxPC-3 and Panc-1 were utilized to examine the level of hydrogen peroxide in the absence or presence of SOD and catalase. [Int J Oncol] Abstract |