Glucagon-stimulated ethanol metabolism in the liver of the rat

Rat liver slices incubated in a Krebs Ringer Bicarbonate (or TRIS) buffer metabolize ethanol at about 80-160 umoles/g x hr. Dinitrophenol (10 mM), an uncoupler of mitochondrial oxidative phosphorylation, stimulated ethanol metabolism by 75%, whereas cyanide (3 mM0, an inhibitor of mitochondrial oxidations, decreased it by about 50%. Glucagon (10√7M) increased ethanol metabolism by about 100%. Glucagon-stimulated ethanol metabolism was inhibited by 10 mM Ouabain, an inhibitor of the sodium pump (from 11.66 +/- 1.37 to 6.83 +/- 0.75 μmoles/g x 5 min), and by 10 μM Atractyloside, an inhibitor of ATP/ADP translocation across the inner mitochondrial membrane (from 10.64 +/- 2.32 to 6.06+/- 2.02 μmoles/g x 5 min). Glucagon also increased the active transport of 87Rb (from 217.25 +/- 31.24 to 354.24 +/- 41.56 mmoles/Kg dry wt x hr) without changing passive transport of this ion. These results suggest that glucagon, by stimulating the activity of the sodium pump, increases the ability of mitochondria to reoxidize reducing equivalents generated during ethanol metabolism, thus accounting for at least one-half of the increased ethanol metabolism observed in the presence of this hormone