HMG-CoA reductase inhibitors do not improve glucose intolerance in spontaneously diabetic Goto-Kakizaki rats.
We examined whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve glucose intolerance in spontaneously diabetic Goto-Kakizaki (GK) rats or not. The fasting blood glucose, plasma insulin, and serum cholesterol levels were significantly higher in GK rats than those in age-matched Wistar rats. All rats were given orally once a day 0.5% carboxymethylcellulose, pravastatin 8 mg/kg, simvastatin 8 mg/kg, or atorvastatin 8 mg/kg. An oral glucose tolerance test (OGTT) was performed before and 3, 6 and 12 weeks after statin treatments. The hyperglycemic response to OGTT in GK rats significantly exceeded that in Wistar rats. The plasma insulin level in GK rats increased with age until 14-week-old (treated for 6 weeks), and then decreased. Glucose intake significantly increased the plasma insulin in almost all rats. The increment of plasma insulin due to OGTT in GK rats appeared to be less than that in Wistar rats, because the basal level was already high in GK rats. Pravastatin, simvastatin, and atorvastatin did not modify changes in blood glucose and plasma insulin induced by glucose intake. In conclusion, long-term treatments of GK rats with statins did not improve glucose intolerance observed during OGTT.
Satoh
Kumi
K
Department of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Japan. kumi@hokuyakudai.ac.jp
Keimatsu
Natsue
N
Kanda
Makoto
M
Kasai
Toshinori
T
Takaguri
Akira
A
Sun
Fan
F
Ichihara
Kazuo
K
D000818:Animals; D000069059:Atorvastatin; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003920:Diabetes Mellitus / Q000235:genetics*; D018149:Glucose Intolerance / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006538:Heptanoic Acids / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000627:therapeutic use
D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin