Starch Source Influences Dietary Glucose Generation at the Mucosal α-Glucosidase Level

The quality of starch digestion, related to the rate and extent of release of dietary glucose, is associated with glycemia-related problems such as diabetes and other metabolic syndrome conditions. Here, we found that the rate of glucose generation from starch is unexpectedly associated with mucosal alpha-glucosidases and not just alpha-amylase. This understanding could lead to a new approach to regulate the glycemic response and glucose-related physiologic responses in the human body. There are six digestive enzymes for starch: salivary and pancreatic alpha-amylases and four mucosal alpha-glucosidases, including N- and C-terminal subunits of both maltase-glucoamylase and sucrase-isomaltase. Only the mucosal alpha-glucosidases provide the final hydrolytic activities to produce substantial free glucose. We report here the unique and shared roles of the individual alpha-glucosidases for alpha-glucans persisting after starch is extensively hydrolyzed by alpha-amylase (to produce alpha-limit dextrins (alpha-LDx)). All four alpha-glucosidases share digestion of linear regions of alpha-LDx, and three can hydrolyze branched fractions. The alpha-LDx, which were derived from different maize cultivars, were not all equally digested, revealing that the starch source influences glucose generation at the mucosal alpha-glucosidase level. We further discovered a fraction of alpha-LDx that was resistant to the extensive digestion by the mucosal alpha-glucosidases. Our study further challenges the conventional view that alpha-amylase is the only rate-determining enzyme involved in starch digestion and better defines the roles of individual and collective mucosal alpha-glucosidases. Strategies to control the rate of glucogenesis at the mucosal level could lead to regulation of the glycemic response and improved glucose management in the human body.