Improvement effect of captopril on insulin resistance mediated by PPARγin vascular endothelial cells
10.3969/j.issn.1001-1978.2015.04.019
- VernacularTitle:PPARγ介导卡托普利改善高糖诱导血管内皮细胞胰岛素抵抗的作用
- Author:
Guoqiang YAN
;
Chunxiang CHUN
;
Fanghui CHEN
;
Yan GAO
;
Jiajia CHU
;
Teng LI
;
Qiren HUANG
- Publication Type:Journal Article
- Keywords:
captopril;
high glucose;
human umbilical vein endothelium cells;
insulin resistance;
PPARγ;
NO;
ET-1
- From:
Chinese Pharmacological Bulletin
2015;(4):532-536,537
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the role of captopril in insulin resistance of endothelial cells induced by high glucose.Methods 1 .Improvement effect of captopril on insulin resistance in HUVECs was observed.The HUVECs were seeded in a 6-well plate and were ran-domly divided into 5 groups,namely,control group, IR group,IR together with different Cap concentrations (low,medium and high concentration),respectively. 2.Improvement effect of Cap on insulin resistance was mediated by PPARγin HUVECs.HUVECs were ran-domly divided into 6 groups,namely,control group, control +PPARγinhibitor (PI)(1 .0 μmol · L -1 ) group,IR group,IR +PI(1 .0 μmol·L -1 )group,IR +Cap(1 ×1 0 -5 mol·L -1 ) group,and IR +Cap +PI (1 .0 μmol·L -1 )group.All indicators were detected. Results After HUVECs were incubated with media containing 33 mmol·L -1 of glucose for 48 h,the NO levels were significantly decreased while ET-1 levels were significantly elevated,showing a significant differ-ence between IR group and control group (P <0.01 ). The expression levels of PPARγmRNA and its protein were somewhat up-regulated,but there was no signifi-cant difference between IR group and control group (P>0.05).When the HUVECs in IR group were treated with DMEM containing glucose (33 mmol·L -1 )for 48 h and insulin for 30 min,the expression levels of PPARγmRNA and its protein in Cap groups were simi-lar to those in the IR group,and there was no signifi-cant difference between the two groups (P >0.05 );however, the expression levels of phosphorylated PPARγprotein in Cap groups were increased compared with IR group (P <0.05).The levels of NO were sig-nificantly increased whereas the levels of ET-1 were decreased in Cap groups,which had significant differ-ences compared with IR group (P <0.05).Nonethe-less,pre-treating with GW9662,a PPARγinhibitor, the improvement effects of Cap were markedly abol-ished.Conclusions Captopril could improve high glucose-induced insulin resistance of endothelial cells mediated by PPARγ,and the underlying mechanisms are related to the activation of PPARγ,rather than its expression.
