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

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.

• Authors: Megu Yamaguchi Baden, Kenji Fukui, Yoshiya Hosokawa, Hiromi Iwahashi, Akihisa Imagawa, Iichiro Shimomura
• Journal: PloS one (PLoS One) Vol. 10 Issue 12 Pg. e0144606 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26659307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• CXCL10 protein, human
• Chemokine CXCL10
• Enzyme Inhibitors
• FAS protein, human
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Interferon Inducers
• Interferon-alpha
• Peptides
• Phosphoinositide-3 Kinase Inhibitors
• Receptors, Virus
• Venoms
• fas Receptor
• Interferon-beta
• Exenatide
• Cyclic AMP-Dependent Protein Kinases
• Poly I-C

Topics

• Antiviral Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Differentiation
• Cells, Cultured
• Chemokine CXCL10 (genetics, metabolism)
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• Enzyme Inhibitors (pharmacology)
• Exenatide
• Gene Expression Regulation
• Glucagon-Like Peptide-1 Receptor (antagonists & inhibitors, genetics, metabolism)
• Humans
• Hypoglycemic Agents (pharmacology)
• Induced Pluripotent Stem Cells (drug effects, metabolism, pathology)
• Insulin-Secreting Cells (drug effects, metabolism, pathology)
• Interferon Inducers (pharmacology)
• Interferon-alpha (genetics, metabolism)
• Interferon-beta (genetics, metabolism)
• Models, Biological
• Peptides (pharmacology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Poly I-C (genetics, pharmacology)
• Receptors, Virus (genetics, metabolism)
• Signal Transduction
• Transfection
• Venoms (pharmacology)
• Virus Diseases (genetics, metabolism, pathology)
• fas Receptor (genetics, metabolism)