Acute suppression of hepatic gluconeogenesis by glucose in the intact animal

Within 2 h after glucose administration to fasting rats the incorporation of radioactive lactate into blood glucose and liver glycogen is decreased. Using tryptophan, which facilitates the study of gluconeogenesis prior to the phosphoenolpyruvate (PEP) carboxykinase step by increasing the level of certain hepatic metabolites, we have found that in animals fasted for 24 h glucose markedly decreased hepatic malate and aspartate concentrations without a corresponding fall in that of pyruvate, suggesting a decrease in pyruvate carboxylase activity. An inhibitor of fatty acid oxidation, 4-pentenoic acid, similarly decreased the accumulation of these intermediates, and octanoic acid significantly lessened the fall in malate and aspartate with glucose. The changes in tissue metabolite levels were consistent with inhibition of the liver pyruvate carboxylase reaction by glucose treatment, and with abolition of this inhibition by octanoate administration. Alanine and glutamate levels in the liver of tryptophan-treated animals were decreased 90 and 32%, respectively, by glucose. Thus, glucose administration in the whole animal acutely decreases gluconeogenesis by apparently inhibiting the pyruvate carboxylase step and decreasing alanine levels in the liver.