Fatty acids and insulin resistance.

We have demonstrated that physiological elevations in plasma free fatty acid concentrations inhibit insulin-stimulated glucose uptake in a dose-dependent manner in normal control subjects and in patients with NIDDM. Two possible mechanisms were identified: 1) a fat-related inhibition of glucose transport or phosphorylation that appeared after 3-4 h of fat infusion and 2) a decrease in muscle glycogen synthase activity that appeared after 4-6 h of fat infusion. We conclude that elevations of plasma FFAs caused insulin resistance and hence may play a significant role in the pathogenesis of insulin resistance in obesity and NIDDM.