Effects of pioglitazone on lipid-induced insulin resistance in rats
- VernacularTitle:吡格列酮对脂质诱导胰岛素抵抗大鼠的影响及其机制研究
- Author:
Gang-Yi YANG
;
Ling ZHANG
;
Ling LI
;
Yi TANG
;
Qing-Ming LI
;
Chao FANG
;
Qin SUN
;
Ke LI
;
Chao-Zhong SHU
;
GUNTHER BODEN
- Publication Type:Journal Article
- Keywords:
Insulin resistance;
Pioglitazone;
Lipids;
Resistin;
Adiponectin
- From:
Chinese Journal of Endocrinology and Metabolism
1986;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of pioglitazone on glucose metabolism,circulating resistin and adiponectin concentrations,and tissue resistin levels in rats with insulin resistance induced by free fatty acid (FFA).Methods A hyperinsulinaemic-euglycaemic clamp and[3-~3H]-glucose tracing technique were used in awake rats.Insulin-mediated peripheral and hepatic glucose metabolism,plasma resistin and adipenectin levels, resistin levels in tissues were assessed by hyperinsulinaemic-euglycaemic clamp with elevation of FFA by lipid infusion over 4 h in rats pretreated with or without pioglitazone.Results During steady-state of clamp,there was a significant increase in plasma FFA in lipid-infused group(L group)and pioglitazone-pretreated lipid-infused group(P/L group)compared to control rats(P<0.01).The glucose infusion rate(GIR)in P/L group was significantly reduced as compared with controls[(20.6?0.9 vs 33.6?1.5)mg?kg~(-1)?min~(-1),P<0.01], whereas the GIR was lower in L group than in P/L group[(12.6?0.8 vs 20.6?0.9)mg?kg~(-1)?min~(-1),P<0.01].As compared with baseline,the hepatic glucose production(HGP)was significantly suppressed by 85% [(18.3?2.1 vs 2.7+2.4)mg?kg~(-1)?min~(-1) and (17.5?2.6 vs 2.6?1.0)mg?kg~(-1)?min~(-1),both P<0.01]during the hyperinsulinaemic clamp in control and P/L groups.The suppressive effect of insulin on HGP was significantly blunted in L group[(17.3?2.1 vs 15.8?1.5]mg?kg~(-1)?min~(-1)].The rate of glucose disappearance(G_(Rd))was reduced in L group and P/L group compared with controls(P<0.01).Baseline plasma resistin level was lower in P/L group than that in the controls[(7.8?1.3 vs 29.1?3.1)?g/L,P<0.01].After lipid infusion,plasma resistin levels significantly increased in P/L group,but remained lower than that of L group [(18.1?3.8 vs 47.0?2.2)?g/L,P<0.01].Baseline adiponectin level was higher in P/L group than those in the controls and L groups[(3.9?0.2 vs 2.8?0.1 and 2.6?0.2)mg/L,P<0.01].After clamp,plasma adiponectin levels were decreased in L group and L/P group compared with baseline(both P<0.05).In addition, the resistin level in the liver of P/L group decreased compared with the controls and L groups(both P<0.05), whereas significantly increased in the muscle of L group.Conclusion Lipid infusion induces an acute insulin- resistance in vivo.Pioglitazone pretreatment partly prevents FFA-induced insulin resistance possibly by changing resistin and adiponectin levels.