Interrelation between the effects of ethanol and thyroid hormones on gluconeogenesis from alanine in perfused rat liver.
Ethanol and thyroid hormones are among various factors that can alter hepatic gluconeogenesis, and the present study was done to determine the interrelation between the influence of ethanol and of T4 on glucose synthesis from alanine in isolated rat liver. With a sufficient supply of alanine, 20 mM ethanol enhanced glyconeogenesis nearly 60% in normal rat liver; higher ethanol concentrations, i.e., 40 or 80 mM, produced no further change in glucose synthesis. In contrast, 20, 40, or 80 mM ethanol had no effect on an already accelerated rate of gluconeogenesis in T4-treated rat liver. the redox state of the liver cytosol, as indicated by the L/P ratio and the alpha-GP/DHAP ratio, was markedly increased by ethanol in normal rat liver and, to a lesser extent, in thyrotoxic rat liver. Ethanol decreased pyruvate, PEP, and 3PGA but increased DHAP, F6P, and G6P concentrations in normal rat liver. In thyrotoxic rat liver per se, the pyruvate level was decreased whereas the levels of intermediates in the gluconeogenic sequence from OAA to 3PGA, and of alanine uptake and on pyruvate conversion to PEP. NADH produced by ethanol oxidation enhanced 3PGA conversion to DHAP in T4-treated as well as in normal rat liver. Despite these effects of ethanol on the gluconeogenic pathway, T4 stimulation of the rate of gluconeogenesis was not affected by ethanol. The results suggest that with an adequate supply of alanine as substrate, ethanol stimulates gluconeogenesis in normal rat liver but has no affect on an already enhanced gluconeogenesis in thyrotoxic rat liver.
D000409:Alanine / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D006980:Hyperthyroidism / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000494:pharmacology*
D000431:Ethanol; D000409:Alanine; D013974:Thyroxine