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 abnormalities in fructose-fed rats, we examined whether an improvement of insulin sensitivity by troglitazone (CS-045) or a decrease in plasma lipids by bezafibrate affects the relationship between serum levels of lipid and glucose. In addition, we also examined changes in liver glycogen metabolism and beta-oxidation in fructose-fed rats. Troglitazone ameliorated fasting hyperlipidemia, hyperglycemia, and hyperinsulinemia. In addition, it augmented glycogen synthase activity by 53%, and decreased the mitochondrial palmitic acid beta-oxidation rate and ketone body production rate by 27% and 55%, respectively. However, hyperglycemia and liver glycogen synthase activity were not improved by bezafibrate treatment despite a marked reduction of serum triglyceride (TG) levels resulting from a 1.76-fold increase in mitochondrial oxidation and a 2.04-fold increase in hepatic ketone body production. These results suggest that abnormalities in glucose and lipid metabolism in fructose-fed rats, which are ameliorated by troglitazone, may be closely linked to reduced glycogen synthase activity in the liver.
Inoue
I
I
Fourth Department of Medicine, Saitama Medical School, Japan.
Takahashi
K
K
Katayama
S
S
Harada
Y
Y
Negishi
K
K
Itabashi
A
A
Ishii
J
J
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004032:Diet; D004361:Drug Tolerance; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000502:physiology*; D006006:Glycogen Synthase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D005632:Fructose; D006006:Glycogen Synthase; D000077288:Troglitazone; D005947:Glucose; D011190:Potassium Cyanide; D001629:Bezafibrate