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Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue

AIMS: 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:...

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Autores principales: Baden, Megu Yamaguchi, Fukui, Kenji, Hosokawa, Yoshiya, Iwahashi, Hiromi, Imagawa, Akihisa, Shimomura, Iichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676675/
https://www.ncbi.nlm.nih.gov/pubmed/26659307
http://dx.doi.org/10.1371/journal.pone.0144606
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author Baden, Megu Yamaguchi
Fukui, Kenji
Hosokawa, Yoshiya
Iwahashi, Hiromi
Imagawa, Akihisa
Shimomura, Iichiro
author_facet Baden, Megu Yamaguchi
Fukui, Kenji
Hosokawa, Yoshiya
Iwahashi, Hiromi
Imagawa, Akihisa
Shimomura, Iichiro
author_sort Baden, Megu Yamaguchi
collection PubMed
description AIMS: 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.
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spelling pubmed-46766752015-12-31 Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue Baden, Megu Yamaguchi Fukui, Kenji Hosokawa, Yoshiya Iwahashi, Hiromi Imagawa, Akihisa Shimomura, Iichiro PLoS One Research Article AIMS: 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. Public Library of Science 2015-12-11 /pmc/articles/PMC4676675/ /pubmed/26659307 http://dx.doi.org/10.1371/journal.pone.0144606 Text en © 2015 Baden et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Baden, Megu Yamaguchi
Fukui, Kenji
Hosokawa, Yoshiya
Iwahashi, Hiromi
Imagawa, Akihisa
Shimomura, Iichiro
Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue
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
title_full Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue
title_fullStr Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue
title_full_unstemmed Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue
title_short Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue
title_sort examination of a viral infection mimetic model in human ips cell-derived insulin-producing cells and the anti-apoptotic effect of glp-1 analogue
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676675/
https://www.ncbi.nlm.nih.gov/pubmed/26659307
http://dx.doi.org/10.1371/journal.pone.0144606
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