REGULATION OF GLUCOSE-UTILIZATION DURING THE INHIBITION OF FATTY-ACIDOXIDATION IN RAT MYOCYTES

The study of the regulation of glucose utilization by inhibition of fa tty acid oxidation is greatly enhanced by the availability of specific inhibitors of fatty acid oxidation. This study examines the regulatio n of cardiac glucose utilization by inhibition of fatty acid oxidation at different sites. The effects of Etomoxir and 4-bromocrotonic acid (4-BCA) on the oxidation of [l-C-14]palmitate, [1-C-14]-octanoate and [U-C-14]glucose were studied in isolated rat myocytes. Fifty percent i nhibition of palmitate oxidation was achieved at 8 mu M Etomoxir and 4 0 mu M 4-BCA. Octanoate oxidation was inhibited only by 4-BCA. In cont rast to their effect on palmitate oxidation, these inhibitors signific antly stimulated the oxidation of glucose in a concentration-dependent manner. Moreover, the oxidation of [2-C-14]pyruvate was increased two -fold by these compounds. The rate of utilization of [U-C-14]-2-deoxyg lucose was also stimulated 2-3 times by these inhibitors. These studie s suggest that the stimulation of glucose utilization via the inhibiti on of fatty acid oxidtion may be mediated through the stimulation of b oth glucose transport and the oxidation of pyruvate by the pyruvate de hydrogenase complex.