Effect of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on triglyceride kinetics in chronically streptozotocin-diabetic rats.
The effect of simvastatin (MK-733, Banyu, Tokyo, Japan), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on triglyceride kinetics, was studied in chronically streptozocin-diabetic rats. Diabetic rats, in whom diabetes was induced by a single intravenous injection of streptozotocin (40 mg/kg body weight) 2 months before the experiment, had significantly higher plasma glucose, triglyceride, and cholesterol levels compared with nondiabetic control rats, but triglyceride secretion rate was not increased. Both triglyceride secretion rate and plasma triglyceride level were significantly suppressed under nonfasting conditions in diabetic rats fed a (0.1%) simvastatin-containing diet for 10 days. After an overnight fast, their triglyceride secretion rate was not suppressed by this diet. However, their plasma triglyceride level was significantly (50%) suppressed, suggesting improved triglyceride removal from the circulation. In diabetic rats, the newly secreted triglyceride-rich lipoprotein particles were significantly cholesterol-enriched, but simvastatin had no effect on their lipid composition. These results suggest that the hypertriglyceridemia seen in chronically diabetic rats is mainly due to a triglyceride-removal defect, and that simvastatin reduces plasma triglyceride levels in these rats both by stimulating triglyceride removal and by reducing its entry into the circulation.
Maeda
E
E
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yoshino
G
G
Matsushita
M
M
Nagata
K
K
Morita
M
M
Murata
Y
Y
Naka
Y
Y
Kazumi
T
T
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D019821:Simvastatin; D014280:Triglycerides / Q000097:blood*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin