Effect of metabolic acidosis on renal gluconeogenesis in vivo

Abstract

A precise method for blood glucose determination was applied to the study of renal glucose production in acidosis. In dogs made acidotic by administration of NH4CI for 3 days, renal venous-arterial glucose difference and glucose production were significantly increased. Renal venous-arterial glucose difference was much smaller than hepatic venous-arterial difference in both acidotic and control dogs, indicating that renal gluconeogenesis contributed relatively little to total body glucose production. The increase in renal glucose output was that which would be expected if much of all of the glutamine giving rise to augmentation of ammonia production in acidosis was ultimately converted to glucose. In the acidotic dogs, renal cortical ghitamate was significantly decreased. These observations are consistent with the hypothesis that metabolic acidosis accelerates a rate-limiting reaction in the renal gluconeogenic pathway at a point between [alpha]-ketoghitarate and glucose, and that the consequent enhancement in conversion of [alpha]-ketoglutarate and glutamate to glucose causes a fall in intracellular glutamate, which effects activation of glutaminase and an increase in production of ammonia from glutamine.