Tohoku J. Exp. Med., 1997, 181 (3)

Slight but Significant Improvement of Insulin Resistance of Wistar Fatty Rats by Treatment with a Disaccharidase Inhibitor, AO-128

MAKATO TOMINAGA1, MAMORU KIMURA2, MASAHIKO IGARASHI2, HIDEYUKI EGUCHI2, KIMIKO IGARASHI2, TAKASHI ABE2, KAZUHIKO SUGIYAMA2, HIDEO MANAKA2 and HIDEO SASAKI2

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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