Mucosal alpha-glucosidase hydrolysis properties and the control of glucogenesis

The mucosal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) have two catalytic α-glucosidases each at C- and N-terminal domains (ctMGAM, ntMGAM, ctSI, and ntSI). These four α-glucosidases are involved in the digestion of glycemic carbohydrates (e.g., starch and sucrose) to monosaccharides in the small intestine. In this research, the hydrolytic properties of mucosal α-glucosidases on glycemic carbohydrates were investigated with the aim to control the rate of glucogenesis. First, individual α-glucosidases were tested with disaccharides of various α-glycosidic linkages and compositional types, and were found to respond differently. Also, maltase activity was competitively inhibited in the presence of sucrose, particularly in the case of ctMGAM. Second, hydrolytic properties of the four α-glucosidases on differently α-amylolyzed starches were demonstrated. Partially hydrolyzed WCS was preferably hydrolyzed by ctMGAM, while fully α-amylolyzed WCS (α-limit dextrins) was hydrolyzed by all four α-glucosidases. These results suggest that inhibition of the ctMGAM reaction may lead to a delay in initial glucose release in the duodenum and proximal jejunum that would both moderate the glycemic peak and extend digestion distally. Third, highly branched structures were enzymatically-synthesized from WCS to demonstrate slow digesting properties at the four α-glucosidases levels. The study revealed that the rate of glucogenesis was decelerated when there was a high proportion of branched α-limit dextrins and a high degree of branching. Fourth, the concept of toggling through differential inhibition of α-glucosidases was applied to examine refined control on glucogenesis with the goal of slow glucose delivery to the body rather than total inhibition. Notably, the α-glucosidases were differently inhibited by the inhibitors. These findings can potentially be applied to extend postprandial glucose response by controlling α-glucosidase activity related to some common chronic disorders (e.g., Type II diabetes and obesity). Ultimately, these investigations provide an important insight into the mechanism of digestion of glycemic carbohydrates by the four mucosal α-glucosidases, and may be applied to study further the relationship between properties of glucose delivery and physiologic-related responses (e.g., gastric emptying, hormone response, food intake, energy balance)