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 carbohy drate absorption from the small intestine, we studied the effect of a disaccharidase inhibitor, AO-128, on insulin resistance of Wistar fatt y rats. Rats were kept on standard laboratory chow with and without IO ppm of AO-128 for 4 weeks, and then subjected to the glucose clamp. A t 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 mi (mean+/-S.D.), signi ficantly lower than 226+/-72mg/100ml of the rats without AO-128. Durin g 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 m g . 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 (2 0.81+/-3.11 mg . kg(-1). min(-1)). However, the percent suppression of hepatic glucose output was 55.2+/-23.8%, which, though incomplete, wa s significantly higher than 17.4+/-11.2% of rats without AO-128. The p resent study suggested that there were at least two, components of ins ulin resistance, a genetically determined and a poor-glycemic control- related, and that the latter insulin resistance was ameliorated by AO- 128.