DIABETES & PANCREATITIS Restoration of the Unfolded Protein Response in Pancreatic β Cells Protects Mice Against Type 1 Diabetes Researchers identified defects in the expression of unfolded protein response mediators ATF6 and XBP1 in β cells from two different type 1 diabetes (T1D) mouse models and then demonstrated similar defects in pancreatic β cells from T1D patients. [Sci Transl Med] Abstract | Press Release Beta Cell Dysfunction Due to Increased ER Stress in a Stem Cell Model of Wolfram Syndrome To investigate the cause of beta cell failure, researchers used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient beta cells showed increased levels of endoplasmic reticulum stress molecules, and decreased insulin content. [Diabetes] Abstract | Press Release Resident Macrophages Mediate Islet Amyloid Polypeptide-Induced Islet IL-1β Production and Beta Cell Dysfunction In cultured islets, macrophages were required for islet amyloid polypeptide-induced mRNA expression of the pro-inflammatory cytokines IL-1β, tumor necrosis factor-α, and interleukin-6, as well as the anti-inflammatory cytokines interleukin-10 and IL-1 receptor antagonist. [Diabetes] Abstract Arx Polyalanine Expansion in Mice Leads to Reduced Pancreatic α-Cell Specification and Increased α-Cell Death Scientists report that mice with an expansion mutation in the first polyalanine tract of Arx exhibit impaired α-cell specification and maintenance, with gradual α-cell loss due to apoptosis. [PLoS One] Full Article Effect of the Cigarette Smoke Component, 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK), on Physiological and Molecular Parameters of Thiamin Uptake by Pancreatic Acinar Cells Scientists examined the effect of chronic exposure of pancreatic acinar cells in vitro and in vivo to the cigarette smoke component NNK on physiological and molecular parameters of the thiamin uptake process. They showed that chronic exposure of 266-6 cells to NNK leads to a significant inhibition in thiamin uptake. [PLoS One] Full Article Expression, Phosphorylation and Function of the Rab-GTPase Activating Protein TBC1D1 in Pancreatic Beta-Cells Using human and rat beta-cells, researchers showed for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta-cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis. [FEBS Lett] Abstract PANCREATIC CANCER Preclinical Validation of AXL Receptor as a Target for Antibody-Based Pancreatic Cancer Immunotherapy Researchers investigated whether inhibition of AXL activity by specific monoclonal antibodies is efficient in limiting proliferation and migration of pancreatic cancer cells. [Oncogene] Abstract Synergistic Activities of MET/RON Inhibitor BMS-777607 and mTOR Inhibitor AZD8055 to Polyploid Cells Derived from Pancreatic Cancer and Cancer Stem Cells Investigators report the synergistic activity of BMS-777607 in combination with mTOR inhibitor AZD8055 in killing chemoresistant pancreatic cancer and cancer stem cells. [Mol Cancer Ther] Abstract mTOR Plays Critical Roles in Pancreatic Cancer Stem Cells through Specific and Stemness-Related Functions Scientists investigated the significance of the mammalian target of rapamycin (mTOR) pathway in maintaining the properties of pancreatic cancer stem cells. The mTOR inhibitor, rapamycin, reduced the viability of CD133+ pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. [Sci Rep] Full Article |