DIABETES & PANCREATITIS Alternatively Activated Macrophages Promote Pancreatic Fibrosis in Chronic Pancreatitis Unlike acute pancreatitis, scientists found that alternatively activated macrophages are dominant in mouse and human chronic pancreatitis. They also demonstrated that mouse and human pancreatic stellate cells are a source of interleukin (IL)-4/IL-13. [Nat Commun] Abstract Pancreatic Islet APJ Deletion Reduces Islet Density and Glucose Tolerance in Mice The authors assessed the influence of a selective APJ deletion in pancreatic islet cells on islet homeostasis and glucose tolerance in mice. APJ deletion in islet cells resulted in a significantly reduced islet size, density and β-cell mass. [Endocrinology] Abstract Insulin-Like Growth Factor 2 Overexpression Induces Beta-Cell Dysfunction and Increases Beta-Cell Susceptibility to Damage Scientists characterized the effects of insulin-like growth factor 2 (IGF2) on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenoviral-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. [J Biol Chem] Abstract | Full Article Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic Beta Cells: Roles in Regulating Cytosolic Zinc Homeostasis and Insulin Secretion The authors examined the beta cell and islet ZIP transcriptome and show consistent high expression of ZIP6 and ZIP7 genes across human, mouse islets and MIN6 beta cells. Modulation of ZIP6 and ZIP7 expression significantly altered cytosolic zinc influx in pancreatic beta cells, indicating an important role for ZIP6 and ZIP7 in regulating cellular zinc homeostasis. [J Biol Chem] Abstract | Full Article PANCREATIC CANCER Pancreatic Cancer Exosomes Initiate Pre-Metastatic Niche Formation in the Liver Scientists showed that pancreatic ductal adenocarcinoma-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden. [Nat Cell Biol] Abstract | Press Release Targeting Pancreatic Cancer Metastasis by Inhibition of Vav1, a Driver of Tumor Cell Invasion Investigators found that treatment of cultured pancreatic tumor cells with azathioprine inhibited Vav1-dependent invasive cell migration and matrix degradation, through inhibition of Rac and Cdc42 signaling. [Cancer Res] Abstract MicroRNA-33a-Mediated Downregulation of Pim-3 Kinase Expression Renders Human Pancreatic Cancer Cells Sensitivity to Gemcitabine Researchers demonstrated that plasma microRNA (miR)-33a levels positively correlated with miR-33a levels in tumor tissues of patients with pancreatic ductal adenocarcinoma and are a good prognostic indicator of overall survival. Overexpression of miR-33a inhibited tumor cell proliferation and increased the chemosensitivity to gemcitabine both in vitro and in vivo. [Oncotarget] Full Article An Unexpected Inhibition of Antiviral Signaling by Virus-Encoded Tumor Suppressor p53 in Pancreatic Cancer Cells Vesicular stomatitis virus (VSV)-encoded p53 or p53-coiled-coil did not inhibit antiviral signaling in non-malignant human pancreatic ductal cells, which retained their resistance to all tested VSV recombinants. [Virology] Abstract |