Ethanol stimulates glycogenolysis and inhibits both glycogenesis via gluconeogenesis and from exogenous glucose in perfused rat liver

Abstract

Aims: Although it is commonly recognized that ethanol suppresses gluconeogenesis, the influence of alcohol intake on blood glucose levels remains controversial. Ethanol may act on both glucose production and glucose consumption in the liver. Thus, we studied each effect of ethanol on glucose oxidation, gluconeogenesis, glycogenesis and glycogenolysis in the liver.

Methods: The rat liver was isolated and cyclically perfused with a medium containing 50 mmol/l ethanol.

Results: Ethanol enhanced 14C-glucose oxidation in the liver from 1.09 +/- 0.11 to 1.41 +/- 0.14 micromol for 20 min (p < 0.05). Gluconeogenesis from 14C-lactate was markedly reduced by ethanol from 8.0 +/- 1.3 to 1.5 +/- 0.6 micromol for 12 min (p < 0.01). Ethanol increased glycogenolysis (net hepatic glucose output, 0.47 +/- 0.10 vs. 0.22 +/- 0.04 mmol/30 min, p < 0.01), and then decreased hepatic glycogen content (179 +/- 38 vs. 273 +/- 39 mg in the presence of 1 mU/ml insulin after 30 min of perfusion, p < 0.05). Ethanol decreased the direct glycogenesis from 14C-glucose from 0.55 +/- 0.08 to 0.33 +/- 0.05 micromol per 100 mg glycogen for 30 min (p < 0.01). Ethanol inhibited the indirect glycogenesis from 14C-lactate from 0.21 +/- 0.04 to 0.09 +/- 0.01 micromol per 100 mg glycogen for 30 min (p < 0.01).

Discussion: The influence of ethanol on the blood glucose regulation by the liver seems to be different between fasted and fed states. Namely, ethanol has both the hypoglycemic effects through decreased gluconeogenesis and increased glucose oxidation and the hyperglycemic effects through decreased glycogenesis and increased glycogenolysis.