Hepatic redox state and gluconeogenesis from lactate in vivo in the rat

Abstract

To examine the role of the hepatic redox state on the rate of gluconeogenesis the effects of sodium crotonate injection (6 mmol/kg body wt) on rat liver metabolite concentrations and gluconeogenesis from lactate were studied in vivo. Crotonate caused a marked oxidation of cytoplasmic and mitochondrial redox couples; decreases were observed in the ratios of (lactate)/(pyruvate), (glycerol 3 phosphate)/(dihydroxy acetone phosphate), (hydroxybutyrate)/(acetoacetate) and measured (NAD+)/(NADH). Increases occurred in the liver concentrations of all gluconeogenic intermediates from pyruvate through to glucose 6 phosphate, but there was no change in lactate concentration. To determine whether gluconeogenesis from lactate was altered by the more oxidized hepatic redox state L [2 14C]lactic acid was infused into the inferior vena cava (50 μmol/min per kg body wt) and the incorporation of radioactivity into blood glucose was measured. Administration of crotonate transiently decreased the rate of lactate incorporation into glucose but within a few minutes the rate of incorporation returned to that of the controls. The results indicate that in these experiments alteration of the NAD+ NADH systems of cytoplasm and mitchondria to a more oxidized state did not change the rate of gluconeogenesis.