Alpha-lipoic acid increases cardiac glucose oxidation independent of AMP-activated protein kinase in isolated working rat hearts.

Alpha-lipoic acid (ALA) is a naturally occurring enantiomer of lipoic acid and is a cofactor of key metabolic enzyme complexes catalyzing the decarboxylation of alpha-keto acids. It was recently shown that ALA increases insulin sensitivity by activating AMP-activated protein kinase (AMPK) in skeletal muscle. Also, administration of ALA to obese rats increases insulin-stimulated glucose uptake in the whole body. We investigated the metabolic effects of ALA on isolated working rat hearts. ALA (500 microM) stimulated glucose oxidation (157+/-31 nmol.dry wt(-1).min(-1) in control vs 315+/-63 nmol.dry wt(-1).min(-1) in ALA-treated, p<0.05) without affecting glycolysis, lactate oxidation, or palmitate oxidation. Cardiac work was not affected by ALA treatment. The effect of ALA on glucose oxidation was not associated with an activation of AMPK. AMPK activity was 190+/-14 pmol.mg protein(-1).min(-1) in control vs 190+/-16 pmol.mg protein(-1).min(-1) in ALA-treated hearts. This study shows that ALA stimulates glucose oxidation in isolated working rat hearts independent of AMPK activation. The beneficial effects of ALA treatment in diabetic patients may be at least in part related to its effect on glucose metabolism.