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.

Plasma obestatin level was determined in patients with impaired glucose regulation and type 2 diabetes mellitus.The plasma obestatin levels in patients of both groups were significantly decreased as compared with that in controls.Plasma obestatin level was negatively correlated with body mass index,HbA_(1C),waist-to-hip ratio,plasma insulin and HOMA-IR.Obestatin level seems to be related with metabolic disorder.