DIABETES & PANCREATITIS Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production Researchers show that β-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult pancreatic multipotent progenitors cells and bias their production of progeny towards β-cells in mouse and human. [Diabetes] Abstract CTGF Modulates Adult β-Cell Maturity and Proliferation to Promote β-Cell Regeneration in Mice Investigators discovered that in embryos, connective tissue growth factor (CTGF) is necessary for β-cell proliferation, and increased CTGF in β-cells promotes proliferation of immature insulin+ cells. CTGF over-expression, under non-stimulatory conditions, does not increase adult β-cell proliferation. [Diabetes] Abstract Retinoic Acid Receptor Signaling Is Required to Maintain Glucose-Stimulated Insulin Secretion and β-Cell Mass Retinoic acid signaling is required for maintaining a range of cellular processes, including cell differentiation, proliferation, and apoptosis. The authors investigated the actions of all-trans-retinoic acid signaling in pancreatic β-cells of adult mice. [FASEB J] Abstract MiR-200 Is Induced by Thioredoxin-Interacting Protein and Regulates ZEB1 Signaling and Beta Cell Apoptosis Using INS-1 beta cells as well as primary islets, scientists discovered that expression of miR-200 was induced by thioredoxin-interacting protein and by diabetes. They found that miR-200 targeted and decreased zinc finger E-box binding homeobox 1 (Zeb1) and promoted beta cell apoptosis as measured by cleaved caspase-3 levels, Bax/Bcl2 ratio, and TUNEL. [J Biol Chem] Abstract | Full Article | Press Release Deletion of Apoptosis Signal-Regulating Kinase 1 (ASK1) Protects Pancreatic Beta-Cells from Stress-Induced Death but Not from Glucose Homeostasis Alterations under Pro-Inflammatory Conditions Researchers tested whether ASK1 deficiency protects beta-cells from glucolipotoxic conditions and cytokines treatment or from glucose homeostasis alteration induced by endotoxemia. [PLoS One] Full Article Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device Recently, scientists developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, they incorporated a novel approach based on photosynthetically-generated oxygen. [Horm Metab Res] Abstract PANCREATIC CANCER LASP1 Is a HIF-1α Target Gene Critical for Metastasis of Pancreatic Cancer Investigators report that LASP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) where it promotes invasion and metastasis. They found that LASP1 overexpression in PDAC cells was mediated by HIF-1α through direct binding to a hypoxia response element in the LASP1 promoter. [Cancer Res] Abstract Curaxin CBL0137 Eradicates Drug Resistant Cancer Stem Cells and Potentiates Efficacy of Gemcitabine in Preclinical Models of Pancreatic Cancer The efficacy of CBL0137 alone or in combination with current standard of care, gemcitabine, was tested against different models of pancreatic ductal adenocarcinoma in vitro and in mouse models. It was found that CBL0137 alone is a potent inducer of apoptosis in pancreatic cancer cell lines and is toxic not only for proliferating bulk tumor cells, but also for pancreatic cancer stem cells [Oncotarget] Full Article Pharmacological Inhibition and Genetic Knockdown of EPAC1 Reduce Pancreatic Cancer Metastasis In Vivo Scientists investigated the role of EPAC1 in invasion and metastasis of pancreatic ductal adenocarcinoma in vivo, and evaluated the therapeutic potential of EPAC inhibitors as anti-metastasis agents for this neoplasm. [Mol Pharmacol] Abstract | Full Article Effects of Insulin on Human Pancreatic Cancer Progression Modeled In Vitro Researchers examined the effects of a range of insulin doses on signaling, proliferation and survival in three human cell models meant to represent three stages in pancreatic cancer progression: primary pancreatic duct cells, the HPDE immortalized pancreatic ductal cell line, and the PANC1 metastatic pancreatic cancer cell line. [BMC Cancer] Full Article Downregulation of CPE Regulates Cell Proliferation and Chemosensitivity in Pancreatic Cancer The expressions of carboxypeptidase E (CPE) in pancreatic cancer (PC) cell lines and cancer patients were investigated by Western blot and qRT-PCR. In PC cell line BX-pc-3, CPE was downregulated and its effect on cancer cell proliferation, migration, cisplatin chemosensitivity, and in vivo tumor growth was analyzed by Western blot, proliferation assay, invasion assay, and in vivo transplantation, respectively. [Tumor Biol] Abstract |