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

The effects of -carnitine on14CO2release from [1-14C]pyruvate oxidation (an index of pyruvate dehydrogenase activity, PDH), [2-14C]pyruvate, and [6-14C]glucose oxidation (indices of the acetyl-CoA flux through citric acid cycle), and [U-14C]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. -carnitine increased the release of14CO2from [1-14C]pyruvate, and decreased that of [2-14C]pyruvate in a time and concentration-dependent manner. At a concentration of 2.5 m -carnitine produced a 50% increase of CO2release from [1-14C]pyruvate and a 50% decrease from [2-14C]pyruvate oxidation. -carnitine also increased CO2release from [1-14C[pyruvate oxidation by 35%, and decreased that of [2-14C]pyruvate oxidation 30%, in isolated rat heart mitochondria. The fatty acid oxidation inhibitor, etomoxir, stimulated the release of CO2from both [1-14]pyruvate and [2-14C]pyruvate. These results were supported by the effects of -carnitine on the CO2release from [6-14C]- and [U-14C]glucose oxidation. -carnitine (5 m ) decreased the CO2release from [6-14C]glucose by 37%, while etomoxir (50μm) increased its release by 24%. -carnitine had no effect on the oxidation of [U-14C]glucose. -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 -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.