Carnitine and Myocardial Glucose Metabolism

L-carnitine has an important role in the integrated regulation of energy metabolism in muscle. While the role of L-carnitine as a cofactor in the oxidation of long-chain fatty acids has been well established, it is only recently that L-carnitine has been recognized to have an additional important role in the regulation of carbohydrate metabolism. Studies primarily performed in heart tissue have shown that increasing myocardial carnitine concentration can dramatically increase both glucose and lactate oxidation. This effect of carbohydrate metabolism appears to be partly responsible for the observed beneficial effects of L-carnitine in treating a number of pathological conditions. For instance, in hypertrophied hearts and in diabetic hearts increasing tissue levels of carnitine can improve both mechanical function and glucose oxidation. In addition, during reperfusion of hearts following ischemia, L-carnitine also improves heart function and increases glucose oxidation. In many of these pathologies the benefits of L-carnitine occur even though fatty acid oxidation is not impaired, and the effects of L- carnitine are accompanied by an increase in glucose oxidation. Whether the effects of L-carnitine on myocardial metabolism are related to an increase in fatty acid oxidation or to an increase in glucose oxidation probably depends to a large extent on whether a severe tissue carnitine deficiency exists, in which case the primary effect of L-carnitine treatment is probably via an increase in fatty acid oxidation rates. If L-carnitine treatment increases tissue carnitine levels, above relatively normal levels we believe that the primary metabolic effects of L-carnitine are on glucose oxidation. In this chapter, the mechanisms by which L-carnitine alters carbohydrate metabolism will be discussed, as well as the resultant effects on contractile function.