Modulation of Starch Digestion for Slow Glucose Release through Toggling of Activities of Mucosal α-Glucosidases

Starch digestion involves the breakdown by alpha-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal alpha-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). MGAM and SI are anchored to the small intestinal brush-border epithelial cells, and each contains a catalytic N- and C-terminal subunit. All four subunits have alpha-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit has an additional exo-debranching activity on the alpha-1,6-linkage. Inhibition of alpha-amylase and/or alpha-glucosidases is a strategy for treatment of type 2 diabetes. We illustrate here the concept of toggling: differential inhibition of subunits to examine more refined control of glucogenesis of the alpha-amylolyzed starch malto-oligosaccharides with the aim of slow glucose delivery. Recombinant MGAM and SI subunits were individually assayed with alpha-amylolyzed waxy corn starch, consisting mainly of maltose, maltotriose, and branched alpha-limit dextrins, as substrate in the presence of four different inhibitors: acarbose and three sulfonium ion compounds. The IC50 values show that the four alpha-glucosidase subunits could be differentially inhibited. The results support the prospect of controlling starch digestion rates to induce slow glucose release through the toggling of activities of the mucosal alpha-glucosidases by selective enzyme inhibition. This approach could also be used to probe associated metabolic diseases.