917-98 Regulation of Glucose Utilization by L-Carnitine in Cardiac Myocytes

L-Carnitine has been shown to protect the myocardium from ischemic injury, and also improves cardiac function in cardiomyopathies associated with carnitine deficiency and diabetes. However, the exact mechanism whereby carnitine exerts its effect is not fully understood. The present study was designed to investigate the effect of carnitine on the regulation of glucose utilization in the heart. These studies were performed by determining the effect of L-carnitine (5 mM) on the 14 CO 2 release from [1- 14 C]pyruvate (an index of pyruvate dehydrogenase complex, PDH), [2- 14 C]pyruvate (an index of acetyl-CoA flux through Kreb's cycle), and [6- 14 C]glucose (an index of the oxidative utilization of glucose). in rat myocytes. Substrate Rate of Oxidation (nmol/mg protein130 min) Control L-Carnitine [1- 14 C]pyruvate 141.80 ± 8.50 212 ± 28.80 * [2- 14 C]6436pyruvate 39.40 ± 7.90 21.1 ± 4.40 * [6- 14 C]glucose 1.56 ± 0.05 0.95 ± 0.05 * Values are presented as the mean ± SD of at least three different experiments. Asterisks represent a p l 0.05 of the effect of carnitine vs control. These data show that L-carnitine stimulates PDH activity by 50%. However, the flux of acetyl-CoA and glucose through Kreb's cycle was significantly decreased by this compound. These results suggest that L-carnitine enhances the removal of acetyl-CoA produced from glucose metabolism out of the mitochondrial matrix, thereby, activating the PDH complex.