title: Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Megu Yamaguchi
authors.initials: MY
authors.lastname: Baden
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Hosokawa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000077270:Exenatide; D005786:Gene Expression Regulation; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011070:Poly I-C / Q000235:genetics / Q000494:pharmacology; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014688:Venoms / Q000494:pharmacology*; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D054357:Chemokine CXCL10; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007369:Interferon Inducers; D016898:Interferon-alpha; D016899:Interferon-beta; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011070:Poly I-C; D011991:Receptors, Virus; D014688:Venoms; D019014:fas Receptor; C114753:CXCL10 protein, human; C491901:FAS protein, human