Effect of hepatic glucose production on acute insulin resistance induced by lipid-infusion in awake rats.

Abstract

To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats. A hyperinsulinaemic-euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4-h intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral and hepatic glucose metabolism was assessed by hyperinsulinaemic-euglycaemic clamp combined with [3-(3)H]-glucose infusion. During hyperinsulinaemic-euglycaemic clamp, there was a significant increase in plasma free fatty acid (FFA, from 741.9+/-50.6 to 2 346.4+/-238.5 micromol/L, P<0.01) in lipid-infused group. The glucose infusion rates (GIR) in the lipid infusion rats, compared to control rats, were significantly reduced (200-240 min average: lipid infusion; 12.6+/-1.5 vs control; 34.0+/-1.6 mg/kg.min, P<0.01), declining to - 35% of the corresponding control values during the last time of the clamp (240 min: lipid infusion; 12.0+/-1.9 vs control; 34.7+/-1.7 mg/kg.min, P<0.0001). At the end of clamp study, the hepatic glucose production (HGP) in control rats was significantly suppressed (88%) from 19.0+/-4.5 (basal) to 2.3+/-0.9 mg/kg.min (P<0.01). The suppressive effect of insulin on HGP was significantly blunted in the lipid-infused rats (200-240 min: from 18.7+/-3.0 to 23.2+/-3.1 mg/kg.min (P<0.05). The rate of glucose disappearance (GRd) was a slight decrease in the lipid-infused rats compared with controls during the clamp. These data suggest that lipid infusion could induces suppression of hepatic glucose production, impairs the abilities of insulin to suppress lipolysis and mediate glucose utilization in peripheral tissue. Therefore, we conclude that lipid-infusion induces an acute insulin resistance in vivo.