Dichloroacetate Inhibits Peripheral Efflux of Pyruvate and Alanine during Hormonally Simulated Catabolic Stress

Abstract

The purpose of this study was to examine the relationship of peripheral metabolism of glucose, lactate, alanine, and muscle protein catabolism to pyruvate availability during stress. Peripheral catabolic stress was simulated by the infusion of epinephrine, cortisol, and glucagon into the femoral artery of 12 healthy volunteers, 6 of whom received prior treatment with dichloroacetate while 6 served as controls. The catabolic hormone infusion reproduced the peripheral stress response in which glucose consumption increased and the efflux of lactate, alanine, and total amino acid nitrogen (i.e., net muscle protein catabolism) from the leg increased. Dichloroacetate (DCA), which is known to increase pyruvate oxidation, reduced the hormonally stimulated efflux of pyruvate and alanine from the leg and decreased the rate of extremity glucose consumption. DCA had no effect on the rate of lactate efflux and except for alanine had no effect on the stimulated rate of total amino acid nitrogen loss. These results demonstrate the dependance of alanine efflux on pyruvate availability during stress and suggest that the rate of glycolysis within peripheral tissues is a major factor in regulating the quantity of alanine efflux. This study further illustrates that except for alanine, pyruvate kinetics are not salient in the regulation of muscle protein catabolism and elucidates the dichotomy between alanine kinetics and true muscle protein breakdown.