Slight but significant improvement of insulin resistance of Wistar fatty rats by treatment with a disaccharidase inhibitor, AO-128.
To know whether the insulin resistance is improved by delaying carbohydrate absorption from the small intestine, we studied the effect of a disaccharidase inhibitor, AO-128, on insulin resistance of Wistar fatty rats. Rats were kept on standard laboratory chow with and without 10 ppm of AO-128 for 4 weeks, and then subjected to the glucose clamp. At the end of the 4-week treatment, plasma glucose level at 14:00 to 16:00 of AO-128 treated rats was 121 +/- 14 mg/100 ml (mean +/- S.D.), significantly lower than 226 +/- 72 mg/100 ml of the rats without AO-128. During clamp steady state under 20 mU.kg (-1).min (-1) continuous insulin infusion, glucose uptake of AO-128 treated rats was only 7.62 +/- 0.70 mg.kg (-1). min (-1), not different from 6.64 +/- 0.91 mg.kg (-1).min (-1) of rats without AO-128, but much lower than the lean littermates (20.81 +/- 3.11 mg.kg (-1).min (-1)). However, the percent suppression of hepatic glucose output was 55.2 +/- 23.8%, which, though incomplete, was significantly higher than 17.4 +/- 11.2% of rats without AO-128. The present study suggested that there were at least two, components of insulin resistance, a genetically determined and a poor-glycemic control-related, and that the latter insulin resistance was ameliorated by AO-128.
Tominaga
M
M
Department of Laboratory Medicine, Yamagata University, School of Medicine, Japan.
Kimura
M
M
Igarashi
M
M
Eguchi
H
H
Igarashi
K
K
Abe
T
T
Sugiyama
K
K
Manaka
H
H
Sasaki
H
H
D000818:Animals; D001786:Blood Glucose / Q000737:chemistry / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003511:Cyclohexanols / Q000494:pharmacology*; D004186:Disaccharidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005215:Fasting; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D015309:Glucose Clamp Technique; D006029:Glycosuria / Q000652:urine; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014556:Urine
D001786:Blood Glucose; D003511:Cyclohexanols; D007328:Insulin; C054577:AO 128; D004186:Disaccharidases; D005947:Glucose