The postulation that the increased NADH2/NAD ratio generated in the liver cell during ethanol metabolism causes the suppression of hepatic gluconeogenesis has been tested in several ways in twenty-eight fasted glycogendepleted dogs in whom hepatic gluconeogenesis was inhibited by infusions of ethanol. First, it was shown that fructose, a non-NAD-dependent precursor of glucose, produced a rapid restoration of hepatic glucose output during ethanol-induced suppression of hepatic gluconeogenesis. Second, in contrast, the infusion of glutamate and α-ketoglutarate, both NAD-dependent precursors of glucose, failed to augment the depressed rate of hepatic gluconeogenesis induced by ethanol. Finally, the administration of methylene blue, a redox dye which oxidizes NADH2 to NAD, not only prevented the expected fall in hepatic glucose output when infused simultaneously with ethanol, but also produced a rapid restoration of hepatic glucose output previously depressed by ethanol administration in fasting dogs. These data are consonant with the thesis that the increased NADH2/NAD ratio, which characterizes ethanol oxidation by the liver cell, causes a partial block at several points in the gluconeo genic pathway and is responsible for the ethanol-induced suppression of hepatic gluconeogenesis.
Skip Nav Destination
Original Contributions| April 01 1967
Ethanol-induced Hypoglycemia: II. Mechanism of Suppression of Hepatic Gluconeogenesis
Leonard L Madison, MD;
Amanda Lochner, PhD;
Leonard L Madison, Amanda Lochner, Johan Wulff; Ethanol-induced Hypoglycemia: II. Mechanism of Suppression of Hepatic Gluconeogenesis. Diabetes 1 April 1967; 16 (4): 252–258. https://doi.org/10.2337/diab.16.4.252
Download citation file: