DIABETES & PANCREATITIS Expression of Human Cationic Trypsinogen (PRSS1) in Murine Acinar Cells Promotes Pancreatitis and Apoptotic Cell Death Scientists developed a novel transgenic murine model system using wild-type human PRSS1 or two hereditary pancreatitis-associated mutants to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. [Cell Death Dis] Full Article Pancreatic ß-Cell Na+ Channels Control Global Ca2+ Signaling and Oxidative Metabolism by Inducing Na+ and Ca2+ Responses that Are Propagated into Mitochondria Researchers showed that tetrodotoxin inhibits glucose-dependent depolarization and blocks cytosolic Na+ and Ca2+ responses and their propagation into mitochondria. Their results showed that communication of the Na+ channels with mitochondria shape both global Ca2+ and metabolism signals linked to insulin secretion in ß cells. [FASEB J] Abstract Distinct Requirements for Beta-Catenin in Pancreatic Epithelial Growth and Patterning To resolve the potential roles of ß-catenin in development of multipotent pancreatic progenitor cells and ß-cells, scientists generated pancreas- and pre-endocrine-specific ß-catenin knockout mice. Pancreas-specific loss of ß-catenin produced not only a dramatic reduction in acinar cell numbers, but also a significant reduction in ß-cell mass. [Dev Biol] Abstract The Immunoregulation Effect of Alpha 1-Antitrypsin Prolong ß-Cell Survival after Transplantation The authors established a ß cell line (NIT-hAAT) that stably expresses human alpha 1-antitrypsin. Interestingly, in a cytotoxic T lymphocyte-killing assay, they found that hAAT reduced apoptosis and inflammatory cytokine production in NIT-1 cells and regulated the Th1/Th2 cytokine balance in vitro. [PLoS One] Full Article 17ß-Estradiol Protects against Glucosamine-Induced Pancreatic ß-Cell Dysfunction Researchers investigated changes in insulin production and ß-cell apoptosis in pancreatic islets after glucosamine (GlcN) treatment in rats with or without ovariectomy and used MIN-6 cells to investigate the protective effects and molecular mechanisms of 17ß-estradiol in GlcN-induced ß-cell dysfunction. [Menopause] Abstract MANF Is Indispensable for the Proliferation and Survival of Pancreatic ß Cells Scientists generated mesencephalic astrocyte-derived neurotrophic factor (MANF)-deficient mice that strikingly develop severe diabetes due to progressive postnatal reduction of ß cell mass, caused by decreased proliferation and increased apoptosis. [Cell Rep] Full Article | Graphical Abstract PANCREATIC CANCER Impaired c-Jun N-Terminal Protein Kinase Signaling Cooperates with KrasG12D Expression to Accelerate Pancreatic Ductal Adenocarcinoma Researchers demonstrated the cooperative interaction of endogenous expression of KrasG12D with loss-of-function mutations in mitogen-activated protein kinase kinase 4 (mkk4) or both, mkk4 and mkk7 genes in the pancreas. [Cancer Res] Abstract | Full Article CHIP Is a Novel Tumor Suppressor in Pancreatic Cancer through Targeting EGFR Researchers showed that carboxyl terminus of heat shock protein 70-interacting protein (CHIP) interacts and ubiquitinates epidermal growth factor receptor (EGFR) for proteasome-mediated degradation in pancreatic cancer cells, thereby inhibiting the activation of EGFR downstream pathway. [Oncotarget] Abstract Resistance to the Tyrosine Kinase Inhibitor Axitinib Is Associated with Increased Glucose Metabolism in Pancreatic Adenocarcinoma Scientists showed that human cell lines and mouse pancreatic adenocarcinoma cell lines obtained from the spontaneous pancreatic cancer mouse model were sensitive to axitinib. [Cell Death Dis] Full Article Measurement of Protein Kinase B Activity in Single Primary Human Pancreatic Cancer Cells An optimized peptide substrate was used to measure protein kinase B activity in single cells. The system was validated in three model pancreatic cancer cell lines before application to cells from a human pancreatic adenocarcinomas propagated in nude mice. [Anal Chem] Abstract Pancreatic Cancer Stem-Like Cells Display Aggressive Behavior Mediated via Activation of FoxQ1 Researchers found that isolated triple-marker positive cells of human pancreatic cancer MiaPaCa-2 and L3.6pl cells behave as cancer stem-like cells (CSLCs). These CSLCs exhibit aggressive behavior such as increased cell growth, migration, clonogenicity, and self-renewal capacity. [J Biol Chem] Abstract | Full Article |