Mechanisms of fatty acid-induced inhibition of glucose uptake

Abstract

Increased plasma FFA reduce insulin-stimulated glucose up-take. The mechanisms responsible for this inhibition, however, remain uncertain. It was the aim of this study to determine whether the FFA effect was dose dependent and to investigate its mechanism. We have examined in healthy volunteers (13 male/1 female) the effects of three steady state plasma FFA levels (- 50,- 550,- 750 MuM) on rates of glucose uptake, glycolysis (both with 3-3H-glucose), glycogen synthesis (de-termined with two independent methods), carbohydrate (CHO) oxidation (by indirect calorimetry), hepatic glucose output, and nonoxidative glycolysis (glycolysis minus CHO ox-idation) during euglycemic-hyperinsulinemic clamping. In-creasing FFA concentration (from- 50 to- 750 gM) de-creased glucose uptake in a dose-dependent fashion (from- 9