Glucose metabolism in perfused skeletal muscle. Pyruvate dehydrogenase activity in starvation, diabetes and exercise

Abstract

The interconversion of pyruvate dehydrogenase between its inactive phosphorylated and active dephosphorylated forms was studied in skeltal muscle. Exercise, induced by electrical stimulation of the sciatic nerve (5/s), increased the measured activity of (active) pyruvate dehydrogenase 3-fold in intact anesthetized rats within 2 min. No further increase was seen after 15 min of stimulation. In the perfused rat hindquarter, (active) pyruvate dehydrogenase activity was decreased by 50% in muscle of starved and diabetic rats. Exercise produced a 2-fold increase in its activity in all groups; the relative differences between fed, starved and diabetic groups persisted. Perfusion of muscle with acetoacetate (2 mM) decreased (active) pyruvate dehydrogenase activity by 50% at rest but not during exercise. Whole-tissue concentrations of pyruvate and citrate, inhibitors of (active) pyruvate dehydrogenase kinase and (inactive) pyruvate dehydrogenase phosphate phosphatase respectively, were not altered by exercise. A decrease in the ATP/ADP ratio was observed, but did not appear to be sufficient to account for the increase in (active) pyruvate dehydrogenase activity. Interconversion of the phosphorylated and dephosphorylated forms of pyruvate dehydrogenase may play a major role in the regulation of pyruvate oxidation by exercise and by variations in the hormonal and nutritional state. Comparison of enzyme activity with measurements of lactate oxidation in the perfused hindquarter suggest that pyruvate oxidation is also modulated by the concentrations of substrates, cofactors and inhibitors of (active) pyruvate dehydrogenase activity.