Stimulation of Non-oxidative Glucose Utilization by L-carnitine in Isolated Myocytes

Abstract The effects of l -carnitine on 14 CO 2 release from [1- 14 C]pyruvate oxidation (an index of pyruvate dehydrogenase activity, PDH), [2- 14 C]pyruvate, and [6- 14 C]glucose oxidation (indices of the acetyl-CoA flux through citric acid cycle), and [U- 14 C]glucose (an index of both PDH activity and the flux of acetyl-CoA through the citric acid cycle), were studied using isolated rat cardiac myocytes. l -carnitine increased the release of 14 CO 2 from [1- 14 C]pyruvate, and decreased that of [2- 14 C]pyruvate in a time and concentration-dependent manner. At a concentration of 2.5 m m, l -carnitine produced a 50% increase of CO 2 release from [1- 14 C]pyruvate and a 50% decrease from [2- 14 C]pyruvate oxidation. l -carnitine also increased CO 2 release from [1- 14 C[pyruvate oxidation by 35%, and decreased that of [2- 14 C]pyruvate oxidation 30%, in isolated rat heart mitochondria. The fatty acid oxidation inhibitor, etomoxir, stimulated the release of CO 2 from both [1- 14 ]pyruvate and [2- 14 C]pyruvate. These results were supported by the effects of l -carnitine on the CO 2 release from [6- 14 C]- and [U- 14 C]glucose oxidation. l -carnitine (5 m m ) decreased the CO 2 release from [6- 14 C]glucose by 37%, while etomoxir (50 μ m ) increased its release by 24%. l -carnitine had no effect on the oxidation of [U- 14 C]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.