The inhibition of gluconeogenesis following alcohol in humans.

Accurate quantification of gluconeogenic flux following alcohol ingestion in overnight-fasted humans has yet to be reported. [2-13C1]glycerol, [U-13C6]glucose, [1-2H1]galactose, and acetaminophen were infused in normal men before and after the consumption of 48 g alcohol or a placebo to quantify gluconeogenesis, glycogenolysis, hepatic glucose production, and intrahepatic gluconeogenic precursor availability. Gluconeogenesis decreased 45% vs. the placebo (0.56 ± 0.05 to 0.44 ± 0.04 mg ⋅ kg-1 ⋅ min-1vs. 0.44 ± 0.05 to 0.63 ± 0.09 mg ⋅ kg-1 ⋅ min-1, respectively, P < 0.05) in the 5 h after alcohol ingestion, and total gluconeogenic flux was lower after alcohol compared with placebo. Glycogenolysis fell over time after both the alcohol and placebo cocktails, from 1.46-1.47 mg ⋅ kg-1 ⋅ min-1to 1.35 ± 0.17 mg ⋅ kg-1 ⋅ min-1(alcohol) and 1.26 ± 0.20 mg ⋅ kg-1 ⋅ min-1, respectively (placebo, P < 0.05 vs. baseline). Hepatic glucose output decreased 12% after alcohol consumption, from 2.03 ± 0.21 to 1.79 ± 0.21 mg ⋅ kg-1 ⋅ min-1( P < 0.05 vs. baseline), but did not change following the placebo. Estimated intrahepatic gluconeogenic precursor availability decreased 61% following alcohol consumption ( P < 0.05 vs. baseline) but was unchanged after the placebo ( P < 0.05 between treatments). We conclude from these results that gluconeogenesis is inhibited after alcohol consumption in overnight-fasted men, with a somewhat larger decrease in availability of gluconeogenic precursors but a smaller effect on glucose production and no effect on plasma glucose concentrations. Thus inhibition of flux into the gluconeogenic precursor pool is compensated by changes in glycogenolysis, the fate of triose-phosphates, and peripheral tissue utilization of plasma glucose.