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Acta Diabetologica

Erschienen in:

01.04.2013 | Original Article

Thiazolidinediones protect mouse pancreatic β-cells directly from cytokine-induced cytotoxicity through PPARγ-dependent mechanisms

verfasst von: An-ping Wang, Xia Li, Ying Zheng, Bi-lian Liu, Gan Huang, Xiang Yan, Zhenqi Liu, Zhiguang Zhou

Erschienen in: Acta Diabetologica | Ausgabe 2/2013

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Abstract

Since most of the current studies of thiazolidinediones (TZDs) are only focused on improving glycemic control, increasing insulin sensitivity, and regulating inflammatory states in Type 2 Diabetes, it is still controversial whether TZDs have direct, protective effects on pancreatic β-cells in autoimmune diabetes. Here, we show the protective effects of TZDs on mouse pancreatic β-cell line cells (NIT-1) impaired by exposure to inflammatory cytokines (IL-1β and IFN-γ) and explore the potential mechanisms for this. The apoptosis rate and caspase-3 activity were remarkably increased, and insulin secretion response to glucose was impaired severely by exposure to IL-1β/IFN-γ for 48 h compared to control cells, whereas apoptosis rate and caspase-3 activity were significantly decreased in cells with treatment of rosiglitazone (RGZ) or pioglitazone (PIG), and the capacity for insulin secretion response to glucose was recovered. TZDs protect pancreatic β-cells from cytokine-induced cytotoxicity through PPARγ activation. The protective effects of the TZDs on NIT-1 cells disappeared when PPARγ was blocked with PPARγ-siRNA interference or treatment with GW9662, the PPARγ antagonist. Additionally, the enhancement of PPARγ expression by treatment with TZDs inhibited the expression of caspase 3 in IL-1β/IFN-γ-induced NIT-cells. Also, the inhibition of caspase 3 expression by TZDs was blocked by co-treatment with GW9662 or infection with PPARγ-siRNA. Taken together, our data suggest that TZDs might serve to protect pancreatic β-cells directly from cytokine-induced cytotoxicity through a PPARγ-dependent pathway, and caspase-3 may play an important role in the mechanisms involved.

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Titel: Thiazolidinediones protect mouse pancreatic β-cells directly from cytokine-induced cytotoxicity through PPARγ-dependent mechanisms
verfasst von: An-ping Wang
Xia Li
Ying Zheng
Bi-lian Liu
Gan Huang
Xiang Yan
Zhenqi Liu
Zhiguang Zhou
Publikationsdatum: 01.04.2013
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 2/2013
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-010-0239-8

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Thiazolidinediones protect mouse pancreatic β-cells directly from cytokine-induced cytotoxicity through PPARγ-dependent mechanisms

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