Stimulation of non-oxidative glucose utilization by L-carnitine in isolated myocytes

The effects of L-carnitine on ¹⁴CO₂ release 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. L-carnitine increased the release of ¹⁴CO₂ from [1-¹⁴C]pyruvate, and decreased that of [2-¹⁴C]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 [1-¹⁴C]pyruvate and a 50% decrease from [2-¹⁴C]pyruvate oxidation. L-carnitine also increased CO₂ release 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 CO₂ from both [1-¹⁴C]pyruvate and [2-¹⁴C]pyruvate. These results were supported by the effects of L-carnitine on the CO₂ release from [6-¹⁴C]- and [U-¹⁴C]glucose oxidation. L-carnitine (5 mM) decreased the CO₂ release from [6-¹⁴C]glucose by 37%, while etomoxir (50 μM) 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.