5-HOUR FATTY-ACID ELEVATION INCREASES MUSCLE LIPIDS AND IMPAIRS GLYCOGEN-SYNTHESIS IN THE RAT

Insulin-mediated muscle glycogen synthesis is impaired after several w eeks of high-fat feeding in rats, but not by short-term (2-hour) nones terified fatty acids (NEFA) elevation induced by intravenous triglycer ide/heparin infusion (TG/H). We examined whether a longer TG/H infusio n induces defective glycogen synthesis. Five-hour hyperinsulinemic (70 0 pmol/L) euglycemic clamps with either TG/H or saline infusion were p erformed. TG/H-infused rats developed insulin resistance, but only aft er 2 to 3 hours. Red gastrocnemius glycogen synthesis rate decreased b y 50% (P < .01 v saline) associated with decreased glycogen synthase a ctivity (GSa; assessed at several glucose-6-phosphate [G-6-P] levels; two-way ANOVA, P = .02) and increased muscle TG and total long-chain a cyl coenzyme A (LCAC) content (twofold; P < .05 v saline). Thus a 3- t o 5-hour NEFA elevation in the rat produced significant impairment of insulin-stimulated muscle glycogen synthesis, associated with muscle l ipid 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. Copyright (C) 1998 by W.B. Saunders Company.