[Glitazones protects beta cell function from cytotoxic cytokines through PPAR gamma-dependent mechanisms].
OBJECTIVE
To investigate the protective effects of glitazones on islet beta cells and PPAR gamma dependence of such effects.


METHODS
IL-1beta and IFN-gamma were used to treat NIT-1 cells, a beta cell line, to induce beta cell damage. The cells were pretreated with rosiglitazone and pioglitazone at different concentrations to study the protective effects of these drugs. The cell apoptosis rate was determined with Annexin V-FITC by flow cytometry, and the insulin secretion capacity of the cells was assessed with ELISA. GW9662 and PPARgamma-SiRNA were used to specifically inhibit PPAR to investigate the PPAR gamma-dependent mechanisms.


RESULTS
Rosiglitazone and pioglitazone at 10 micromol/L could significantly decrease the apoptosis of beta cells induced by the cytokines (apoptotic rates of 13.99% and 16.67% vs 51.33%, P<0.01). Rosiglitazone at 10 micromol/L and pioglitazone at 20 micromol/L were less effective than 10 micromol/L rosiglitazone and pioglitazone. The insulin secretion of the cytokine-treated cells decreased from 8.5-/+0.6 ng/ml of the control group to 3.6-/+0.5 ng/ml, while rosiglitazone and pioglitazone could increase the insulin secretion to 6.8-/+0.7 ng/ml and 5.9-/+0.9 ng/ml, respectively. When PPAR gamma was specifically inhibited by GW9662 and PPARgamma-SiRNA, the protective effects of rosiglitazone and pioglitazone were almost undetectable, and the apoptotic rate increased and insulin secretion decreased to the level of the cytokine-treated cells.


CONCLUSIONS
Glitazones can protect beta cells from apoptosis and impairment of insulin secretion function resulting from the cytotoxic cytokines via a PPAR gamma-dependent mechanism.
Li
Xia
X
Second Xiangya Hospital, Diabetes Center, Institute of Metabolism and Endocrinology, Central South University, Changsha 410011, China. hellolxwj@yahoo.com.cn
Wang
An-ping
AP
Yan
Xiang
X
Huang
Gan
G
Liu
Bi-lian
BL
Zhou
Zhi-guang
ZG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000009:adverse effects; D053583:Interleukin-1beta / Q000009:adverse effects; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*
D007328:Insulin; D053583:Interleukin-1beta; D047495:PPAR gamma; D045162:Thiazolidinediones; D007371:Interferon-gamma