[Inhibitory effects of thiazolidinedione upon cytokine-induced apoptosis in pancreatic beta-cell line].
OBJECTIVE
To investigate the protective effects and potential mechanisms of TZD upon pancreatic beta-cells.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wang
An-Ping
AP
Diabetes Center & Metabolic Syndrome Research Center, Institute of Metabolism & Endocrinology, Central South University, Changsha 410011, China.
Li
Xia
X
Liu
Bi-Lian
BL
Zheng
Ying
Y
Zheng
Chao
C
Lin
Jian
J
Huang
Gan
G
Yan
Xiang
X
Peng
Jian
J
Zhou
Zhi-Guang
ZG
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D015536:Down-Regulation; D004336:Drug Antagonism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*
D053583:Interleukin-1beta; D045162:Thiazolidinediones; D007371:Interferon-gamma