AN ALPHA-GLUCOSIDASE INHIBITOR, AO-128, RETARDS CARBOHYDRATE-ABSORPTION IN RATS AND HUMANS

The present study was designed to determine the possible significance of a therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the breath hydrogen concentration, which is an index of the amount of unabsorbed carbohydrate in the large intestine, Post-prandi al hyperglycemia is common among diabetic patients. AO-128, a potent a lpha-glucosidase inhibitor, suppressed post-prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of 0.2 mg with each meal. These volunteers increased the breath hydrogen concentration in response to ingestion of non-absorbable lactulose, but decreased only slightly its concentration from the basal level after sucrose ingestio n, indicating complete absorption, When AO-128 (0.2 mg) was given with sucrose, hydrogen production increased only slightly compared with pl acebo, suggesting that the inhibitory effect of AO-128 on sucrose abso rption was minimal, Only 5 g of the 100 g of sucrose was not absorbed and this 5% reduction is too small to explain the observed inhibitory effect on the post-prandial rise in plasma glucose, Sucrose loading in rats (about 443 mg) sharply increased blood glucose and was accompani ed by the rapid disappearance of sucrose from the upper small intestin e, AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small in testinal absorption, but did not induce an influx of sucrose into the cecum and large intestine, while the higher dose (0.1 mg/kg) caused an increased influx of sucrose into the large bowel. These results indic ated that AO-128 retards the absorption of carbohydrate and reduces po st-prandial hyperglycemia.