exenatide and Virus-Diseases

Viral infection is associated with pancreatic beta cell destruction in fulminant type 1 diabetes mellitus. The aim of this study was to investigate the acceleration and protective mechanisms of beta cell destruction by establishing a model of viral infection in pancreatic beta cells.. Polyinosinic:polycytidylic acid was transfected into MIN6 cells and insulin-producing cells differentiated from human induced pluripotent stem cells via small molecule applications. Gene expression was analyzed by real-time PCR, and apoptosis was evaluated by caspase-3 activity and TUNEL staining. The anti-apoptotic effect of Exendin-4 was also evaluated.. Polyinosinic:polycytidylic acid transfection led to elevated expression of the genes encoding IFNα, IFNβ, CXCL10, Fas, viral receptors, and IFN-inducible antiviral effectors in MIN6 cells. Exendin-4 treatment suppressed the elevated gene expression levels and reduced polyinosinic:polycytidylic acid-induced apoptosis both in MIN6 cells and in insulin-producing cells from human induced pluripotent stem cells. Glucagon-like peptide-1 receptor, protein kinase A, and phosphatidylinositol-3 kinase inhibitors counteracted the anti-apoptotic effect of Exendin-4.. Polyinosinic:polycytidylic acid transfection can mimic viral infection, and Exendin-4 exerted an anti-apoptotic effect both in MIN6 and insulin-producing cells from human induced pluripotent stem cells.

Topics: Antiviral Agents; Apoptosis; Cell Differentiation; Cells, Cultured; Chemokine CXCL10; Cyclic AMP-Dependent Protein Kinases; Enzyme Inhibitors; Exenatide; fas Receptor; Gene Expression Regulation; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Induced Pluripotent Stem Cells; Insulin-Secreting Cells; Interferon Inducers; Interferon-alpha; Interferon-beta; Models, Biological; Peptides; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Poly I-C; Receptors, Virus; Signal Transduction; Transfection; Venoms; Virus Diseases