Brief Reports
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 1, 2004; 10(21): 3208-3211
Published online Nov 1, 2004. doi: 10.3748/wjg.v10.i21.3208
Effect of hepatic glucose production on acute insulin resistance induced by lipid-infusion in awake rats
Ling Li, Gang-Yi Yang
Ling Li, Department of Clinical Biochemistry, Chongqing Medical University, Chongqing 400016, China
Gang-Yi Yang, Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
Author contributions: All authors contributed equally to the work.
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 Foundation of China Education Ministry, No. 2003-406
Correspondence to: Dr. Gang-Yi Yang, Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. yanggangyi@hotmail.com
Telephone: +86-23-68486115 Fax: +86-23-68486115
Received: November 18, 2003
Revised: December 1, 2003
Accepted: December 8, 2003
Published online: November 1, 2004
Abstract

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 2346.4 ± 238.5 μmol/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.

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.

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