STIMULATION OF NONOXIDATIVE GLUCOSE-UTILIZATION BY L-CARNITINE IN ISOLATED MYOCYTES

The effects of L-carnitine on (CO2)-C-14 release from [1-C-14]pyruvate oxidation (an index of pyruvate dehydrogenase activity, PDH), [2-C-14]pyruvate, and [6-C-14]glucose oxidation (indices of the acetyl-CoA nux through citric acid cycle), and [U-14C]glucose (an index of both PDH activity and the nux of acetyl-CoA through the citric acid cycle), were studied using isolated rat cardiac myocytes. L-carnitine increased the release of (CO)-C-14, from [1-C-14]pyruvate, and decreased that of [2-C-14]pyruvate in a time and concentration-dependent manner. At a concentration of 2.5 mM, L-carnitine produced a 50% increase of CO2 release from [1-C-14]pyruvate and a 50% decrease from [2-C-14]pyruvate oxidation. L-carnitine also increased CO2 release from [1-C-14]pyruvate oxidation by 35%, and decreased that of [12-C-14]pyruvate oxidation 30%, in isolated rat heart mitochondria. The fatty acid oxidation inhibitor, etomoxir, stimulated the release of CO2 from both [1-(14)]pyruvate and [2-C-14]pyruvate. These results were supported by the effects of L-carnitine on the CO2 release from [6-C-14]- and [U-C-14]glucose oxidation. L-carnitine (5 mM) decreased the CO2 release from [6-C-14]glucose by 37%, while etomoxir (50 mu M) increased its release by 24%. L-carnitine had no effect on the oxidation of [U-14C]glucose. L-carnitine increased palmitate oxidation in a time- and concentration-dependent manner in myocytes. Also, it increased the rate of efflux of acetylcarnitine generated from pyruvate in myocytes. These results suggest that L-carnitine stimulates pyruvate dehydrogenase complex activity and enhances non-oxidative glucose metabolism by increasing the mitochondrial acetylcarnitine efflux in the absence of exogenous fatty acids. (C) 1995 Academic Press Limited