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Five-hour fatty acid elevation increases muscle lipids and impairs glycogen synthesis in the rat


Insulin-mediated muscle glycogen synthesis is impaired after several weeks of high-fat feeding in rats, but not by short-term (2-hour) nonesterified fatty acids (NEFA) elevation induced by intravenous triglyceride/heparin infusion (TG/H). We examined whether a longer TG/H infusion induces defective glycogen synthesis. Five-hour hyperinsulinemic (700 pmol/L) euglycemic clamps with either TG/H or saline infusion were performed. TG/H-infused rats developed insulin resistance, but only after 2 to 3 hours. Red gastrocnemius glycogen synthesis rate decreased by 50% (P < .01 v saline) associated with decreased glycogen synthase activity (GSa; assessed at several glucose-6-phosphate [G-6-P] levels; two-way ANOVA, P=.02) and increased muscle TG and total long-chain acyl coenzyme A (LCAC) content (twofold; P < .05 v saline). Thus a 3- to 5-hour NEFA elevation in the rat produced significant impairment of insulin-stimulated muscle glycogen synthesis, associated with muscle lipid accumulation. These effects were similar to those observed after several weeks of fat feeding. The 5-hour TG/H-infused rat is a useful model for studying lipid-induced muscle insulin resistance.

Type Journal
ISBN 0026-0495 (Print)
Authors Chalkley, S. M.;Hettiarachchi, M.;Chisholm, D. J.;Kraegen, E. W. :
Responsible Garvan Author Prof Edward Kraegen
Published Date 1998-01-01
Published Volume 47
Published Issue 9
Published Pages 1121-6
Status Published in-print
URL link to publisher's version