Inhibitory effects of thiazolidinedione upon cytokine-induced apoptosis in pancreatic beta-cell line
Wang, A.-P.; Li, X.; Liu, B.-L.; Zheng, Y.; Zheng, C.; Lin, J.; Huang, G.; Yan, X.; Peng, J.; Zhou, Z.-G.
Zhonghua Yi Xue Za Zhi 89(28): 1989-1993
2009
ISSN/ISBN: 0376-2491 PMID: 19950576 Document Number: 634680
To investigate the protective effects and potential mechanisms of TZD upon pancreatic beta-cells. Apoptosis was induced in vitro by interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma). After treatment with rosiglitazone (RSG)/pioglitazone (PIG) at the final concentrations of 1 micromol/L, 10 micromol/L, 20 micromol/L respectively, the apoptotic rate of NIT-1 cells was determined by Hoechest33342 staining and Annexin V-FITC/PI flow cytometry respectively. Caspase-3 specific activity of NIT-1 cells was determined by Caspase-3 assay and insulin secretion measured by ELISA. After treatment of different concentrations of RSG/PIG, the apoptotic rate of NIT-1 cells decreased to 29.3%, 14.0%, 28.1% and 27.4%, 16.7%, 23.5% respectively. There were significant differences in apoptotic rate between the RSG/PIG treatment group and IL-1beta/IFN-gamma group (P < 0.01). After treatment with RSG/PIG, glucose-stimulated insulin secretion (GSIS) of NIT-1 cells recovered in different degrees [(6.8 +/- 0.7) ng/ml, (5.9 +/- 0.9) ng/ml, P < 0.01]. There were significant differences in GSIS between the RSG/PIG treatment group and IL-1beta/IFN-gamma group (P < 0.01). Moreover, most of the protective effects of TZD upon pancreatic beta-cells could be blocked by a PPAR-gamma inhibitor, GW9662. TZD might protect pancreatic beta-cells directly via inhibiting cytokine-induced apoptosis and recovering insulin secretion. And the mechanism may be correlated with the down-regulation of caspase-3 activity.