Inhibitory mechanism of acarbose and 1-deoxynojirimycin derivatives on carbohydrases in rat small intestine.

The inhibitory action and mechanism of inhibition of two types of alpha-glucosidase inhibitors, acarbose (Bay-g-5421) and 1-deoxynojirimycin derivatives (Bay-m-1099 and Bay-o-1248), on small intestinal carbohydrases (sucrase, isomaltase, glucoamylase, trehalase and lactase) and pancreatic alpha-amylase were compared in vitro using small intestinal brush border membranes and pancreatic homogenates from adult Sprague-Dawley rats. Acarbose at a low (4 microM) concentration strongly inhibited the activities of glucoamylase, alpha-amylase and sucrase (98, 68, and 63%, respectively). At a high (200 microM) concentration, isomaltase activity was also inhibited (28%); effects on trehalase and lactase activities were negligible. Both the 1-deoxynojirimycin derivatives were even more potent inhibitors of sucrase (Ki = 8.6 x 10(-8) M for Bay-m-1099;Ki = 5.0 X 10(-8) M for Bay-o-1248) than acarbose (Ki = 9.9 x 10(-7) M). Whereas glucoamylase activity was strongly inhibited by the 1-deoxynojirimycin derivatives, alpha-amylase activity was not. In contrast to acarbose, the 1-deoxynojirimycin derivatives at high concentrations (20-200 microM) inhibited considerably trehalase and lactase (a beta-galactosidase) activities. The inhibition of lactase activity was stronger by Bay-m-1099 (Ki = 4.9 X 10(-6) M) than by Bay-o-1248 (Ki = 6.7 X 10(-5) M). Where inhibition was seen, kinetic analysis showed fully competitive inhibition of sucrase, isomaltase, trehalase, glucoamylase and lactase by all three inhibitors.