Impaired glucose tolerance related to changes in the energy metabolism of the remnant liver after major hepatic resection.

In 70% hepatectomized rabbits, the glucose tolerance patterns after an oral glucose load were characterized by a longstanding increase of blood glucose for more than 180 min (a linear pattern) at 24 hr after hepatectomy and by a return toward normal range within 180 min (a parabolic pattern) at 96 hr later. At the linear stage, the concentrations of pyruvate and lactate of the remnant liver increased to 192% and 203%, respectively, of sham-operated controls at 1 hr after an oral glucose load. At 3 hours after glucose load, the concentrations of glucose-6-phosphate, fructose-6-phosphate, pyruvate, and lactate increased to 191%, 192%, 174% and 298%, respectively. By contrast, at the parabolic stage, no significant changes were observed. On the other hand, the energy charge level of the remnant liver decreased to 0.767 at the linear stage and returned to near normal levels at the parabolic stage. The ketone body ratio (acetoacetate/beta-hydroxybutyrate) in the arterial blood decreased to 0.415 at the linear stage, concomitant with the increase in total ketone body and NEFA concentrations, and returned to near normal levels at the parabolic stage. These findings suggest that the reduced mitochondrial redox potential, reflected by the decrease in ketone body ratio, inhibits pyruvate dehydrogenase. This prevents the entrance of pyruvate into the Krebs cycle and results in the inhibition of glucose oxidation, leading to a linear pattern after an oral glucose load.