FATTY-ACIDS AND INSULIN-RESISTANCE

We have demonstrated that physiological elevations in plasma free fatt y acid concentrations inhibit insulin-stimulated glucose uptake in a d ose-dependent manner in normal control subjects and in patients with N IDDM. Two possible mechanisms were identified. 1) a fat-related inhibi tion of glucose transport or phosphorylation that appeared after 3-4 h of fat infusion and 2) a decrease in muscle glycogen synthase activit y that appeared after 4-6 h of Eat infusion. We conclude that elevatio ns of plasma FFAs caused insulin resistance and hence may play a signi ficant role in the pathogenesis of insulin resistance in obesity and N IDDM.