AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats. METHODS: A hyperinsulinaemic-euglycaemic clamp was established in awake chronically ca...AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats. METHODS: 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-^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 2346.44±238.5μmol/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; 12.64±1.5 vs control; 34.04±1.6 mg/kg.min, P<0.01), declining to - 35% of the corresponding control values during the last time of the clamp (240min: lipid infusion; 12.04±1.9 vs control; 34.74±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 19.04±4.5 (basal) to 2.34±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 18.74±3.0 to 23.24±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.CONCLUSION: 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.展开更多
PPAR（peroxisome proliferator-activated receptor) is a family of nuclear receptor.In recent years,it has been focused for the discovery and development of new drugs which are mediated by PPARs.Fibrate hypolipidemic dr...PPAR（peroxisome proliferator-activated receptor) is a family of nuclear receptor.In recent years,it has been focused for the discovery and development of new drugs which are mediated by PPARs.Fibrate hypolipidemic drugs are the specific and potent ligands to PPAR alpha and have been widely used for the treatment of hyperlipidemia.But these drugs induce hepatocarcinogenesis in rodent animals after the long-term administration.However,there are species differences on these phenomena which are not seen in mammals ioncluding human.To clarify the mechanism of carcinogenesis by these drugs in important for the evaluation of safety of these drugs in human.展开更多
基金Supported by the National Natural Science Foundation of China,No.30270631,No.30370671,Science Foundation of Chongqing Health Bureau.No.99-3002 and Applied Basic Research Foundation of Chongqing Science and Technology Committee,No.02-34 and Science Founda
文摘AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats. METHODS: 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-^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 2346.44±238.5μmol/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; 12.64±1.5 vs control; 34.04±1.6 mg/kg.min, P<0.01), declining to - 35% of the corresponding control values during the last time of the clamp (240min: lipid infusion; 12.04±1.9 vs control; 34.74±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 19.04±4.5 (basal) to 2.34±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 18.74±3.0 to 23.24±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.CONCLUSION: 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.
文摘PPAR（peroxisome proliferator-activated receptor) is a family of nuclear receptor.In recent years,it has been focused for the discovery and development of new drugs which are mediated by PPARs.Fibrate hypolipidemic drugs are the specific and potent ligands to PPAR alpha and have been widely used for the treatment of hyperlipidemia.But these drugs induce hepatocarcinogenesis in rodent animals after the long-term administration.However,there are species differences on these phenomena which are not seen in mammals ioncluding human.To clarify the mechanism of carcinogenesis by these drugs in important for the evaluation of safety of these drugs in human.
