Effect of Alcohol on Glucose Production and Lactate, Pyruvate and Ketone Body Metabolism by the Isolated Perfused Rat Liver

Abstract

The purpose of these experiments was to determine whether the effect of ethanol on glucose production could be dissociated from its effect on the cytoplasmic DPN/DPNH ratio in the presence of adequate substrate. Isolated rat livers were perfused with a Krebs bicarbonate Ringer buffer containing 4 per cent albumin and 10 mM alanine in the presence of increasing concentrations of ethanol. Lactate, pyruvate, B-hydroxybutyrate and acetoacetate were used to reflect the cellular redox state. Despite producing maximum changes in lactate, pyruvate and ketone body metabolism, 10 mM ethanol did not inhibit glucose production. Ethanol concentrations of 20 and 40 mM produced no further change in the production of lactate and pyruvate but significantly inhibited ketone body and glucose production by the isolated perfused rat liver. These results are compatible with the proposal that increased entry and intramitochon-drial oxidation of DPNH which results from alcohol metabolism inhibits oxidation of fatty acids, acetyl CoA generation and subsequently gluconeogenesis.