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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.

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