Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats.
The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.
Yasuda
K
K
The Laboratory of Metabolism, Faculty of Integrated Human Studies, Kyoto University, Sakyo-ku, Japan. yasuda@tom.life.h.kyoto-u.ac.jp
Shimowada
K
K
Uno
M
M
Odaka
H
H
Adachi
T
T
Shihara
N
N
Suzuki
N
N
Tamon
A
A
Nagashima
K
K
Hosokawa
M
M
Tsuda
K
K
Seino
Y
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004186:Disaccharidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007294:Inositol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D012333:RNA, Messenger; D007294:Inositol; D000469:Alkaline Phosphatase; D004186:Disaccharidases; C102817:voglibose