DIABETES Diabetes Increases Mortality after Myocardial Infarction by Oxidizing CaMKII Scientists developed a knockin mouse model of oxidation-resistant Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) (MV-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. [J Clin Invest] Full Article | Press Release Regulation of Neurod1 Contributes to the Lineage Potential of Neurogenin3+ Endocrine Precursor Cells in the Pancreas Researchers investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. [PLoS Genet] Full Article Species-Specific Vesicular Monoamine Transporter 2 (VMAT2) Expression in Mammalian Pancreatic Beta Cells: Implications for Optimizing Radioligand-Based Human Beta Cell Mass (BCM) Imaging in Animal Models Since reports on tetrabenazine (TBZ)-based VMAT2 imaging in rodent pancreas have been fraught with confusion, the authors compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimize TBZ imaging in humans. [Diabetelogia] Abstract Osteocalcin Reverses Endoplasmic Reticulum Stress and Improves Impaired Insulin Sensitivity Secondary to Diet-Induced Obesity through Nuclear Factor-κB Signaling Pathway Mice fed a high-fat diet and receiving osteocalcin showed reduced body weight gain, less fat pad gain, and improved insulin sensitivity as well as increased energy expenditure compared with mice fed a high-fat diet and receiving vehicle. Meanwhile, increased endoplasmic reticulum stress, defective insulin signaling, and mitochondrial dysfunction induced by obesity were also effectively alleviated by treatment with osteocalcin. [Endocrinology] Abstract Regulation of NOX-1 Expression in Beta Cells: A Positive Feedback Loop Involving the Src-Kinase Signaling Pathway Regulation of NADPH oxidase-1 (NOX-1) expression in beta cells followed modulation of cellular reactive oxygen species (ROS); pro-oxidants increased NOX-1 and anti-oxidants decreased NOX-1. Activation of Src-kinase followed ROS elevation. Inhibition of Src-kinase decreased NOX-1 expression. [Mol Cell Endocrinol] Abstract PANCREATIC CANCER Strengthened Glycolysis under Hypoxia Supports Tumor Symbiosis and Hexosamine Biosynthesis in Pancreatic Adenocarcinoma Using a well-defined mouse model of pancreatic cancer, researchers report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. [Proc Natl Acad Sci USA] Abstract Heparin-Binding Epidermal Growth Factor-Like Growth Factor Eliminates Constraints on Activated Kras to Promote Rapid Onset of Pancreatic Neoplasia Researchers demonstrated that two oncogenic events, mutation of Kras and production of the growth factor heparin-binding epidermal growth factor-like growth factor, are sufficient for rapid and complete neoplastic transformation of the exocrine pancreas. [Oncogene] Abstract Protein Kinase Cα Inhibitor Protects against Downregulation of Claudin-1 during Epithelial-Mesenchymal Transition of Pancreatic Cancer Scientists investigated the mechanisms of regulation of Snail and claudin-1 via a PKCα signal pathway during epithelial-mesenchymal transition in pancreatic cancer cells and in normal human pancreatic duct epithelial cells. [Carcinogenesis] Abstract Notch Signaling Pathway Targeted Therapy Suppresses Tumor Progression and Metastatic Spread in Pancreatic Cancer Scientists investigated the in vivo therapeutic effect of PF-03084014, a selective γ-secretase inhibitor, alone and in combination with gemcitabine in pancreatic cancer xenografts. PF-03084014 treatment inhibited the cleavage of nuclear Notch 1 intracellular domain and Notch targets Hes-1 and Hey-1. [Cancer Lett] Abstract Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Researchers investigated a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. [PLoS One] Full Article |