Impaired glucose uptake and intact gluconeogenesis in perfused rat liver after carbon tetrachloride injury.
The dynamics of glucose movement across perfused livers were assessed in carbon tetrachloride (CCl4)-injured rats. Rats were given CCl4 for 8 weeks and became glucose intolerant and hyperinsulinemic. The fasted rat liver was cyclically perfused with 4 mM lactate and various concentrations (0-20 mM) of glucose for 20 min. In the CCl4-injured liver, net glucose output was less suppressed at high glucose levels than in the normal liver (147 +/- 70 vs 18 +/- 10 mumol at 20 mM glucose, P < 0.05). Deposition of the carbon from [14C] glucose into glycogen was stimulated at high glucose levels and was markedly reduced in the CCl4-injured liver compared to the normal liver (0.58 +/- 0.33 mumol vs 1.44 +/- 0.20 mumol at 20 mM, P < 0.01). Conversion of [14C] lactate to [14C] glucose was not different between the CCl4-injured and the normal liver at each glucose level. Deposition of the carbon from [14C] acetate into glycogen in the CCl4-injured liver was larger than that in the normal liver at 0 mM glucose (0.81 +/- 0.15 mumol vs 0.32 +/- 0.06 mumol, P < 0.01), but was similar to the normal at 20 mM glucose. In the CCl4-injured liver, utilization of exogenous glucose was impaired at high glucose levels, and gluconeogenetic activity was not impaired at low glucose levels. These changes in the hepatic glucose metabolism seem to account for postprandial hyperglycemia without fasting hypoglycemia associated with liver diseases.
Mokuda
O
O
Third Department of Internal Medicine, Teikyo University School of Medicine, Chiba, Japan.
Ubukata
E
E
Sakamoto
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D019344:Lactic Acid; D002251:Carbon Tetrachloride; D005947:Glucose