Ethanol stimulates glycogenolysis in livers from fed rats.
To determine the reason for the lack of a hypoglycemic effect of ethanol in the fed state, the effect of ethanol on glucose turnover, liver glycogenolysis, and glucose metabolites was determined. Chronically catheterized awake and freely moving fed rats received either ethanol (blood ethanol, 37 +/- 10 mmol/liter, n = 11) or saline (n = 13) intravenously for 4 hr. Glucose turnover was determined using a primed continuous infusion of [3-3H]glucose. The liver was freeze clamped at 4 hr for glycogen and metabolite measurements. Plasma glucose (5.8 +/- 0.3 mmol/liter vs 6.3 +/- 0.2 mmol/liter at 4 hr, ethanol versus saline) and the rate of glucose turnover (61 +/- 9 vs 58 +/- 8 moles/kg.min) were similar during the ethanol and saline infusions. Plasma lactate was significantly higher in the ethanol (1.32 +/- 0.05 mmol/liter) than in the saline (0.86 +/- 0.06 mmol/liter, P less than 0.001) study. Concentrations of gluconeogenic intermediates in the liver (glucose 6-phosphate, fructose 6-phosphate, glucose 1-phosphate, and pyruvate) were all significantly and -30% lower in ethanol-infused than in saline-infused rats. The liver citrate content was similar in ethanol-infused than in saline-infused rats. The liver citrate content was similar in ethanol (0.38 +/- 0.03 mmol/liter) and saline (0.37 +/- 0.04 mmol/liter) studies. Liver glycogen was 75% lower in the ethanol-infused (61 +/- 9 mmol/kg dry wt) than the saline (242 +/- 27 mmol/kg dry wt, P less than 0.001)-infused rats. These data demonstrate that in fed rats given ethanol, glucose turnover is maintained constant by accelerated glycogenolysis. Thus, inhibition of gluconeogenesis by ethanol does not lower hepatic glucose production unless compensatory glycogenolysis can be prevented.
Kubota
M
M
Second Department of Medicine, Helsinki University, Finland.
Virkamäki
A
A
Yki-Järvinen
H
H
D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005636:Fructosephosphates / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000096:biosynthesis; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D005636:Fructosephosphates; D005958:Glucosephosphates; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D011773:Pyruvates; D019344:Lactic Acid; D000431:Ethanol; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D019289:Pyruvic Acid; C031590:glucose-1-phosphate; D005947:Glucose