DIABETES & PANCREATITIS NADPH Oxidase-Dependent Reactive Oxygen Species Stimulate β-Cell Regeneration through Differentiation of Endocrine Progenitors in Murine Pancreas Researchers showed that ROS levels were dynamically changed during pancreas development concomitant with endocrine cell differentiation induced by modest exogenous ROS in rudiment cultures. NOX4 but not NOX2, the member of NADPH oxidase, was expressed persistently in endocrine lineage and showed higher activity in the critical pancreas development phase. [Antioxid Redox Signal] Abstract Sirtuin 6 Regulates Glucose-Stimulated Insulin Secretion in Mouse Pancreatic Beta Cells To investigate the function of Sirtuin 6 (SIRT6) in pancreatic beta cells, researchers performed Sirt6 gene knockdown in MIN6 cells and generated pancreatic- and beta cell-specific Sirt6 knockout mice. [Diabetologia] Abstract Rac-Mediated Actin Remodeling and Myosin II Are Involved in KATP Channel Trafficking in Pancreatic β-Cells Scientists showed that the signaling mechanisms that mediate actin cytoskeleton remodeling are closely associated with AMP-activated protein kinase-induced KATP channel trafficking. Using F-actin staining with Alexa 633-conjugated phalloidin, they observed that dense cortical actin filaments present in INS-1 cells cultured in glucose were disrupted by glucose deprivation or leptin treatment. [Exp Mol Med] Full Article PANCREATIC CANCER TLR9 Ligation in Pancreatic Stellate Cells Promotes Tumorigenesis Researchers showed that Toll-like receptor (TLR)9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. [J Exp Med] Abstract A Novel Protein Isoform of the RON Tyrosine Kinase Receptor Transforms Human Pancreatic Duct Epithelial Cells Scientists report the discovery of a novel RON isoform discovered in human pancreatic cancer. Expression of partial splicing of exons 5 and 6 in immortalized human pancreatic duct epithelial cells activates downstream AKT, and in human pancreatic epithelial nestin-expressing cells, activates both the AKT and MAPK pathways. [Oncogene] Abstract The Retinoic Acid Derivative, ABPN, Inhibits Pancreatic Cancer through Induction of Nrdp1 Investigators showed that the retinoic acid derivative, ABPN, exhibits more potent anticancer effects than erlotinib, while exhibiting less toxicity toward non-cancerous human control cells. [Carcinogenesis] Abstract Integrated Stress Response Is Critical for Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma Scientists used pancreatic cancer cells that are highly resistant to gemcitabine (Gem) and an orthotopic mouse model to investigate the role of the integrated stress response in Gem chemoresistance. [Cell Death Dis] Full Article Up-Regulation of HER2 by Gemcitabine Enhances the Antitumor Effect of Combined Gemcitabine and Trastuzumab Emtansine Treatment on Pancreatic Ductal Adenocarcinoma Cells Out of five tested human pancreatic ductal adenocarcinoma cell lines, including MIA PaCa-2, three showed increases in HER2 expression after gemcitabine (GEM) treatment. The binding of T-DM1 to GEM-treated MIA PaCa-2 cells was higher than to untreated MIA PaCa-2 cells. Treatment with GEM and T-DM1 showed synergic cytotoxic effects on MIA PaCa-2 cells in vitro. [BMC Cancer] Full Article |