EFFECT OF TROGLITAZONE (CS-045) AND BEZAFIBRATE ON GLUCOSE-TOLERANCE,LIVER-GLYCOGEN SYNTHASE ACTIVITY, AND BETA-OXIDATION IN FRUCTOSE-FED RATS

To clarify the relationship between lipid and glucose metabolism abnor malities in fructose-fed rats, we examined whether an improvement of i nsulin sensitivity by troglitazone (CS-045) or a decrease in plasma li pids by bezafibrate affects the relationship between serum levels of l ipid and glucose. In addition, we also examined changes in liver glyco gen metabolism and beta-oxidation in fructose-fed rats. Troglitazone a meliorated fasting hyperlipidemia, hyperglycemia, and hyperinsulinemia . In addition, it augmented glycogen synthase activity by 53%, and dec reased the mitochondrial palmitic acid beta-oxidation rate and ketone body production rate by 27% and 55%, respectively. However, hyperglyce mia and liver glycogen synthase activity were not improved by bezafibr ate treatment despite a marked reduction of serum triglyceride (TG) le vels resulting from a 1.76-fold increase in mitochondrial oxidation an d a 2.04-fold increase in hepatic ketone body production. These result s suggest that abnormalities in glucose and lipid metabolism in fructo se-fed rats, which are ameliorated by troglitazone, may be closely lin ked to reduced glycogen synthase activity in the liver. Copyright (C) 1995 by W.B. Saunders Company