Effects Of Pioglitazone On Lipid-Induced Insulin Resistance In Rats And It Mechanism

Objective: To investigate the effect of Pioglitazone on glucose metabolism, circulating resistin and adiponectin concentrations in free fatty acid –induced insulin resistance in rats. Methords: Male Sprague-Dawley rats was divided into three groups at random : control group ( N group), lipid-infused group (L group) and pioglitazone-treated+lipid-infused group (P/Lgroup). Hyperinsulinemic euglycaemic clamp and [3-3H]-glucose tracing technique were used in awake rats. Insulin-mediated peripheral and hepatic glucose metabolism, plasma resistin and adiponectin levels were assessed by hyperinsulinaemic-euglycaemic clamp with elevation free fatty acids (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 free fatty acid (FFA) in two lipid-infused groups, compared with control rats (P<0.01). The glucose infusion rates (GIR) in pioglitazone-treated rats, compared with controls, were significantly reduced (20.6±0.4 vs.33.6±0.6 mg·kg-1·min-1 P < 0.01), whereas the GIR was lower in the lipid group than in the pioglitazone- treated group (12.6±0.8 vs. 20.6±0.4 mg·kg-1·min-1,P < 0.01). The hepatic glucose production (HGP) of control rats was significantly suppressed (71%) from 18.3±2.1 (basal) to 5.6±1.4 mg·kg-1·min-1 ( P < 0.01), and P/Lgroup was suppressed (85%) from 17.5±2.6 to 2.6±1.0 mg·kg-1·min-1 (P < 0.01) .during the hyperinsulinemic clamp in control and pioglitazone-treated groups. The suppressive effect of insulin on HGP was significantly blunted in the lipid-infused rats (from 17.3±2.1 to 15.8±1.5 mg·kg-1·min-1). The rate of glucose disappearance (GRd) was significantly reduced in two lipid-infused rats compared with controls(23.2±0.9 and 26.6±1.6 vs.41.7±3.0mg·kg-1·min-1, P < 0.01). Baseline resistin levels were significantly lower in the P/L group than the controls (7.8±1.3 vs. 31.5±4.2μg/L, P<0.01). After lipid infusion, plasma resistin levels were significantly increased in the P/L group but remained lower than the P/L group (18.1±3.8 vs.47±3.8μg/L, P<0.01). Baseline adiponectin levels were significantly higher in the P/L group than the control and L groups (3.9±0.2 vs.2.8±0.1 and 2.6±0.2mg/L, P<0.01). After clamp, plasma adiponectin levels were significantly decreased in the L and P/L groups compared with baseline (all P<0.05). P/L groups significantly increased than the L group(3.0±0.1 vs.2.1±0.1mg/L, P < 0.01). Conclusion: Lipid-infusion induces an acute insulin-resistance in vivo. TZDs pretreatment probably prevented partly FFA-induced insulin resistance by changing plasma resistin and adiponectin levels .