STIMULATION BY ALPHA-LIPOIC ACID OF GLUCOSE-TRANSPORT ACTIVITY IN SKELETAL-MUSCLE OF LEAN AND OBESE ZUCKER RATS

alpha-Lipoic acid (ALA), a potent biological antioxidant, improves ins ulin action of skeletal muscle glucose transport and metabolism in bot h human and animal models of insulin resistance. In order to obtain fu rther insight into the potential intracellular mechanisms for the acti on of ALA on insulin-stimulated glucose transport in skeletal muscle, we investigated the effects of direct incubation with ALA (2 mM) on e- deoxyglucose (2-DG) uptake by epitrochlearis muscle from either insuli n-sensitive lean (Fal-) or insulin-resistant obese (falfa) Zucker rats . ALA stimulated 2-DG uptake in muscle of lean animals by 76%, whereas ALA stimulated 2-DG uptake by only 48% in muscle from obese animals. The stimulation of 2-DG uptake due to ALA was enhanced 30-55% in the p resence of insulin. In contrast, ALA action on 2-DG uptake was not add itive with the effects of electrically-stimulated muscle contractions in either insulin-sensitive or insulin-resistant muscle. Wortmannin (1 mu M), an inhibitor of phosphotidylinositol-3-kinase, completely inhi bited insulin action on 2-DG uptake, but inhibited ALA action by only 25%. Collectively these results indicate that although a portion of AL A action on glucose transport in mammalian skeletal muscle is mediated via the insulin signal transduction pathway, the majority of the dire ct effect of ALA on skeletal muscle glucose transport is insulin-indep endent.