DIABETES Pancreatic Islet Musculature Adapts to Insulin Resistance through Dilation and Not Angiogenesis To determine if islet vascularization changes in response to insulin resistance, researchers investigated three independent models of insulin resistance: ob/ob, GLUT4+/-, and mice with high-fat diet-induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased but intra-islet vessel density was decreased as the result of insulin resistance. [Diabetes] Abstract Development of the Human Pancreas from Foregut to Endocrine Commitment Researchers studied the expression profiles of key lineage-specific markers to understand differentiation and morphogenetic events during human pancreas development. In addition to revealing a number of disparities in timing between human and mouse development, these data, directly assembled from human tissue, allow combinations of transcription factors to define sequential stages and differentiating pancreatic cell-types. [Diabetes] Abstract Enhanced Beta Cell Function and Anti-Inflammatory Effect after Chronic Treatment with the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin in an Advanced-Aged Diet-Induced Obesity Mouse Model To explore the long-term effects of dipeptidyl peptidase-4 inhibition on insulin secretion and beta cell mass, researchers have generated a high-fat diet-induced-obesity model in mice of advanced age. Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets. [Diabetologia] Abstract | Press Release Induction of an Antiviral State and Attenuated Coxsackievirus Replication in Type III Interferon Treated Primary Human Pancreatic Islets Researchers showed that human islets respond to a Coxsackievirus serotype B3 infection by inducing the expression of type III interferons (IFNs). They also demonstrated that islet endocrine cells from non-diabetic individuals express the type III IFN receptor subunits IFNλR1 and IL-10R2. [J Virol] Abstract Fibroblast Growth Factor Receptor Like-1 (FGFRL1) Interacts with SHP-1 Phosphatase at Insulin Secretory Granules and Induces Beta-Cell ERK1/2 Activation Researchers determined beta-cell expression of FGFRL1 as well as consequent effects on FGFR1 signaling and biological responses. They confirmed FGFRL1 expression at the plasma membrane and within distinct intracellular granules of both primary beta and βTC3 cells. [J Biol Chem] Abstract | Full Article A Self-Defeating Anabolic Program Leads to β Cell Apoptosis in ER Stress-Induced Diabetes via Regulation of Amino Acid Flux The authors report that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. [J Biol Chem] Abstract | Full Article PANCREATIC CANCER Heparanase Promotes Lymphangiogenesis and Tumor Invasion in Pancreatic Neuroendocrine Tumors Scientists investigated the role of heparanase in pancreatic neuroendocrine tumors (PanNETs) using patient samples and the RIP1-Tag2 PanNET-transgenic mouse model. High heparanase expression significantly correlated with more advanced tumor stage, higher tumor grade and the presence of distant metastasis in PanNET patients. [Oncogene] Abstract Triptolide Induces the Expression of miRNA-142-3p: A Negative Regulator of Heat Shock Protein 70 and Pancreatic Cancer Cell Proliferation Researchers investigated the mechanism by which triptolide inhibits heat shock protein 70 (HSP70). As microRNAs (miRNAs) are becoming increasingly recognized as negative regulators of gene expression, they tested whether triptolide regulates HSP70 via miRNAs. They showed that triptolide, as well as quercetin but not gemcitabine, upregulated miRNA-142-3p in pancreatic ductal adenocarcinoma cells. [Mol Cancer Ther] Abstract Ex Vivo Analysis of Pancreatic Cancer-Infiltrating T Lymphocytes Reveals that ENO-Specific Tregs Accumulate in Tumor Tissue and Inhibit Th1/Th17 Effector Cell Functions Scientists characterized the effector functions of α-enolase (ENO)1-specific T cells isolated from pancreatic cancer patients, and they specifically evaluated the successful role of intra-tumoral T helper 17 (Th17) cells and the inhibitory role of regulatory T (Tregs) cells in respectively promoting or reducing the cancer-specific immune response. [Cancer Immunol Immun] Abstract Norepinephrine Inhibits the Migratory Activity of Pancreatic Cancer Cells Pancreatic cancer cells show a reduced migratory activity upon norepinephrine treatment. By means of their three-dimensional, collagen-based cell migration assay, the authors have investigated the signal transduction pathways involved in this phenomenon. They found that this conflicting effect of norepinephrine on pancreatic cancer cells is due to an imbalanced activation of the two pathways that usually mediate a pro-migratory effect of norepinephrine in other tumor cell types. [Exp Cell Res] Abstract |