Stimulation by α-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats

Erik J. Henriksen, Stephan Jacob, Ryan S. Streeper, Donovan L. Fogt, Jason Y. Hokama, Hans J. Tritschler

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

α-Lipoic acid (ALA), a potent biological antioxidant, improves insulin action of skeletal muscle glucose transport and metabolism in both human and animal models of insulin resistance. In order to obtain further insight into the potential intracellular mechanisms for the action of ALA on insulin-stimulated glucose transport in skeletal muscle, we investigated the effects of direct incubation with ALA (2 mM) on 2-deoxyglucose (2-DG) uptake by epitrochlearis muscle from either insulin-sensitive lean (Fal-) or insulin-resistant obese (fa/fa) 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 presence of insulin. In contrast, ALA action on 2-DG uptake was not additive with the effects of electrically-stimulated muscle contractions in either insulin-sensitive or insulin-resistant muscle. Wortmannin (1 μM), an inhibitor of phosphotidytinositol-3-kinase, completely inhibited insulin action on 2-DG uptake, but inhibited ALA action by only 25%. Collectively, these results indicate that although a portion of ALA action on glucose transport in mammalian skeletal muscle is mediated via the insulin signal transduction pathway, the majority of the direct effect of ALA on skeletal muscle glucose transport is insulin-independent.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalLife Sciences
Volume61
Issue number8
DOIs
StatePublished - Jul 18 1997

Keywords

  • Epitrochlearis muscle glucose transport
  • Insulin action
  • Wortmannin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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