NUTRITIONAL AND HORMONAL-REGULATION OF PYRUVATE METABOLISM IN THE LIVER

The effect of fasting, glucose and glucagon injection on pyruvate metabolism of rat liver mitochondria was studied. Fasting for 24 h caused a 2-fold increase in mitochondrial pyruvate uptake, 5-fold increase in CO2 fixation and no change in pyruvate decarboxylation. Injection of glucose to fasted rats 2 h prior to preparation suppressed by 1/2 the increase in mitochondrial pyruvate uptake and CO2 fixation and increased hepatic pyruvate content. Injection of glucagon together with glucose abolished the depression of pyruvate uptake by glucose but did not prevent the decrease in mitochondrial CO2 fixation or hepatic ketone content caused by glucose alone. The effects of insulin injection resembled that of glucose in decreasing hepatic ketone content, but differed by increasing pyruvate uptake without much change in CO2 fixation. The increase in gluconeogenesis induced by fasting is due to an increase in pyruvate uptake and carboxylation by hepatic mitochondria. The latter is due to the increased mobilization and oxidation of fatty acids induced by reciprocal changes in insulin and glucagon.