DIABETES Identification of Metabolic Modifiers That Underlie Phenotypic Variations in Energy-Balance Regulation This proof-of-concept study indicates that common regulatory GIP variants impart a difference in glucose-dependent insulinotropic polypeptide and glucose metabolism. The study also provides a rare example that identified the common variant-common phenotypic variation pattern based on evidence of moderate gene–environmental interactions. [Diabetes] Retinoic Acid-Inducible Protein I- and MDA5-Initiated Innate Immunity Linked with Adaptive Immunity Accelerates Beta Cell Death in Fulminant Type 1 Diabetes Findings demonstrate the presence of specific innate immune responses to enterovirus infection connected with enhanced adoptive immune pathways responsible for aggressive beta cell toxicity in fulminant type 1 diabetes. [Diabetes] Chronic Methylglyoxal Infusion by Minipump Causes Pancreatic Beta Cell Dysfunction and Induces Type 2 Diabetes in Sprague-Dawley Rats In pancreatic beta cells, methylglyoxal (MG) and MG + L-buthionine sulfoximine reduced insulin secretion, pancreatic duodenal homeobox-1, MafA, GLUT-2, and glucokinase expression; increased C/EBP(beta), nuclear factor-kappaB, MG-induced AGE, N(epsilon)-carboxymeythyllysine, and receptor for advanced glycation end products expression; and caused apoptosis. [Diabetes] Glucose Metabolism-Related Protein 1 (GMRP1) Regulates Pancreatic Beta Cell Proliferation and Apoptosis via Activation of Akt Signaling Pathway in Rats and Mice Overproduction of GMRP1 promoted beta cell proliferation via increased phosphorylation of Akt. Knockdown of Gmrp1 (also known as Btbd10) reduced phosphorylation of Akt with enhanced beta cell apoptosis. [Diabetologia] Cellular Hypoxia of Pancreatic Beta Cells Due to High Levels of Oxygen Consumption for Insulin Secretion In Vitro Researchers examined the effect of insulin secretion on cellular oxygen tension in vitro. [J Biol Chem] ATF2 Interacts with Beta Cell-Enriched Transcription Factors, MafA, Pdx1, and Beta2, and Activates Insulin Gene Transcription Data indicate that ATF2 is an essential component of the positive regulators of the insulin gene expression. [J Biol Chem] Endothelial Cells in Co-Culture Enhance Embryonic Stem Cell Differentiation to Pancreatic Progenitors and Insulin-Producing Cells Through BMP Signaling Results indicate that the differentiation of embryoid bodies to pancreatic progenitors and insulin-producing cells can be enhanced by endothelial cells in vitro and that bone morphogenetic protein pathway activation is central to this process. [Stem Cell Rev] Essential Role of Clusterin in Pancreas Regeneration Researchers suggest that clusterin plays a critical role to promote both exocrine and endocrine regeneration following pancreas injury, as well as for in vitro beta cell regeneration. [Dev Dyn] PANCREATIC CANCER Pancreatic Cancer Cells Respond to Type I Collagen by Inducing Snail Expression to Promote Membrane Type 1-Matrix Metalloproteinase Dependent Collagen Invasion Data demonstrate that pancreatic cancer cells increase Snail on encountering collagen-rich milieu, and suggest that the desmoplastic reaction actively contributes to pancreatic ductal adenocarcinoma progression. [J Biol Chem] Context Dependence of Checkpoint Kinase 1 as a Therapeutic Target for Pancreatic Cancers Deficient in the BRCA2 Tumor Suppressor Researchers established an RNA interference screen to identify genes whose depletion selectively inhibits the growth of cells lacking BRCA2, and then studied the effects of the genetic depletion or pharmacologic inhibition of one candidate, the checkpoint kinase CHK1, in the context of pancreatic cancer. [Mol Cancer Ther] Slug Enhances Invasion Ability of Pancreatic Cancer Cells Through Upregulation of Matrix Metalloproteinase-9 and Actin Cytoskeleton Remodeling Results suggest that Slug promotes migration and invasion of PANC-1 cells, which may correlate with the reorganization of matrix metalloproteinase-9 and remodeling of the F-actin cytoskeleton, but not with E-cadherin expression. [Lab Invest] |