Effects of Free Fatty Acids on Glucose Uptake and Utilization in Healthy Women

To study effects of sex on free fatty acid (FFA)-induced insulin resistance, we have examined the effects of acute elevations of plasma FFA levels on insulin-stimulated total body glucose uptake in nine healthy young women. Euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamps were performed for 4 h with coinfusion of either lipid/heparin (L/H) to acutely raise plasma FFA levels (from approximately 600 to approximately 1,200 micro mol/l) or saline/glycerol to lower fatty acids (from approximately 600 to approximately 50 micro mol/l). L/H infusion inhibited insulin-stimulated glucose uptake (determined with [3-(3)H]glucose) and glycogen synthesis by 31 and 40%, respectively (P < 0.01), almost completely abolished insulin suppression of endogenous glucose production (EGP) (13.6 vs. 10.0 micro mol x kg(-1) x min(-1), NS), prevented the insulin induced increase in carbohydrate oxidation (8.1 vs. 7.4 micro mol x kg(-1) x min(-1), NS), and stimulated fat oxidation (from 3.6 to 5.1 micro mol x kg(-1) x min(-1), P < 0.01). These data showed that acute increases in plasma FFA levels inhibited the actions of insulin on glucose uptake, glycogen synthesis, and EGP in women to a degree similar to that previously reported in men. We conclude that at insulin and FFA levels in the postprandial range, women and men were susceptible to FFA-induced peripheral and hepatic insulin resistance.