Slight but Significant Improvement of Insulin Resistance of Wistar Fatty Rats by Treatment with a
Disaccharidase Inhibitor, AO-128
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MAKATO TOMINAGA1, MAMORU
KIMURA2, MASAHIKO
IGARASHI2, HIDEYUKI
EGUCHI2, KIMIKO
IGARASHI2, TAKASHI ABE2,
KAZUHIKO SUGIYAMA2, HIDEO
MANAKA2 and HIDEO
SASAKI2
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1Department of Laboratory Medicine and 2Third Department of Internal Medicine,
Yamagata University School of Medicine, Yamagata 990-23
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:OO to 16:OO 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.
Key words---
disaccharidase inhibitor; AO-128; insulin resistance; Wistar fatty rats; glucose clamp
Tohoku J. Exp. Med., 1997, 181, 353-360
Address for reprints:
Makoto Tominaga, M.D., Department of Laboratory Medicine, Yamagata University School of Medicine,
2-2-2 Iida-Nishi, Yamagata 990-23, Japan.
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