CARBON TETRACHLORIDE-INDUCED CIRRHOSIS IN RATS - INFLUENCE OF THE ACUTE EFFECTS OF THE TOXIN ON GLUCOSE-METABOLISM

In animal models, conflicting results on the effect of cirrhosis on gl ucose metabolism have been reported. The use of various toxins as well as differences in experimental protocols may be responsible for these controversial data. However, differences may also be explained by the fact that glucose metabolism has been evaluated following different t ime intervals after cessation of the toxic injury. Therefore, we have performed intravenous glucose tolerance tests, euglycemic hyperinsulin emic clamps (at 2, 6, and 30 mU/kg . min insulin infusion rates), and determination of peripheral tissue glucose metabolic index (by [H-3]2- deoxy-glucose injection) in rats treated for 10 weeks with carbon tetr achloride, either 3 days (acute group) or 2 weeks (delayed group) afte r the last CCl4 dose was administered. Cirrhosis was confirmed by live r histological analysis, and by a 22% (P < .05) decrease in C-13-amino pyrine demethylation. In the acute group, whole-body glucose disposal was decreased at the highest insulin infusion rate only (19.7 +/- 1.2 vs. 23.4 +/- 1.2 mg/kg . min in controls, P < .05). In contrast, resul ts of the delayed group were not different from controls at any insuli n infusion rate. Peripheral tissue glucose metabolic index was signifi cantly decreased in all muscles tested in the acute group compared wit h controls. A significant decrease of glucose utilization was found in some but not all muscles in the delayed group but was less pronounced than in the acute group. In conclusion, this study showed that insuli n sensitivity in cirrhotic rats is time dependent with regard to the l ast CCl4 administration. These results must be taken into account when using this experimental model of liver cirrhosis.