AIM:To explore the influence of hepatic glucose productionon acute insulin resistance induced by a lipid infusion in awakerats.METHODS:A hyperinsulinaemic-euglycaemic clamp wasestablished in awake chronically catheterized rats.Two groupsof rats were studied either with a 4-h intraarterial infusion oflipid/heparin or saline.Insulin-mediated peripheral and hepaticglucose metabolism was assessed by hyperinsulinaemic-euglycaemic clamp combined with[3-~3H]-glucose infusion.RESULTS:During hyperinsulinaemic-euglycaemic clamp,there was a significant increase in plasma free fatty acid(FFA,from 741.9±50.6 to 2346.4+238.5 μmol/L,P<0.01)inlipid-infused group.The glucose infusion rates(GIR)in thelipid infusion rats,compared to control rats,were significantlyreduced(200-240 min average:lipid infusion;12.6±1.5 vscontrol;34.0±1.6 mg/kg.min,P<0.01),declining to-35%of the corresponding control values during the last time ofthe 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 wassignificantly suppressed(88%)from 19.0±4.5(basal)to2.3±0.9 mg/kg·min(P<0.01).The suppressive effect ofinsulin on HGP was significantly blunted in the lipid-infusedrats(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 aslight decrease in the lipid-infused rats compared with controlsduring the clamp.CONCLUSION:These data suggest that lipid infusion couldinduces suppression of hepatic glucose production,impairsthe abilities of insulin to suppress lipolysis and mediate glucoseutilization in peripheral tissue.Therefore,we conclude thatlipid-infusion induces an acute insulin resistance in vivo.Li L,Yang GY.Effect of hepatic glucose production on acuteinsulin resistance induced by lipid-infusion in awake rats.World JGastroenterol 2004;10(21):3208-3211http://www.wjgnet.com/1007-9327/10/3208.asp AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awakerats. METHODS: A hyperinsulinaemic-euglycaemic clamp wasestablished 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- ~ 3H] -glucose infusion .RESULTS: During hyperinsulinaemic-euglycaemic clamp, there was a significant increase in plasma free fatty acid (FFA , from 741.9 ± 50.6 to 2346.4 + 238.5 μmol / L, P <0.01) inlipid-infused group. The glucose infusion rates (GIR) in thelipid infusion rats, compared to control rats, were significantlyreduced (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 wassignificantly suppressed (88%) from 19.0 ± 4.5 (basal) to 2.3 ± 0.9 mg / kg · min (P <0.01) suppressive effect of insulin on HGP was significantly blunted in the lipid-infusedrats (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 as light decrease in the lipid-infused rats compared with controls on the clamp. CONCLUSION: These data suggest that lipid infusion could induce inhibition of hepatic glucose production, impairsthe abilities of insulin to suppress lipolysis and mediate glucose administration in peripheral tissue. Before, we conclude that lipid-infusion induces an acute insulin resistance in vivo. Li L, Yang GY. Effect of hepatic glucose production on acuteinsulin resistance induced by lipid-infusion in awake rats. World JGastroenterol 2004; 10 (21): 3208-3211 http: //www.wjgnet.com/1007 -9327 / 10 / 3208.asp