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

Abstract

For digestion of starch, α‐amylase first hydrolyzes the starch structure to α‐limit dextrins (αLDx's). Complete hydrolysis to glucose then takes place through the combined action of mucosal maltase‐glucoamylase (MGAM) and sucrase‐isomaltase (SI), which have two subunits each (N‐ and C‐ terminal). In this study, we applied the concept of “toggling” through differential inhibition of subunits to examine control of glucogenesis from αLDx's with the aim of attaining slow glucose delivery to the body. Mammalian recombinant MGAM and SI subunits were individually reacted with αLDx's with varying concentrations of acarbose, a well known α‐glucosidase inhibitor. Released glucose amounts were analyzed for hydrolysis activity. Notably, results showed selective inhibitory effect on C‐terminal subunits by acarbose for starch digestion. Furthermore, Ki values of C‐terminal subunits were lower than human α‐amylases which can be applied that certain amount of acarbose had inhibitory effect on the hydrolysis of αLDx's by C‐terminal subunits but not on α‐amylase for moderating glucogenesis. This result supports the concept of controlling starch digestion rate for slow glucose release through the “toggling” of activities of the mucosal α‐glucosidases by selective enzyme inhibition. Conceivably this approach could be used to treat Type II diabetes by extending postprandial blood glucose delivery to the body, and may apply as well to other metabolic syndrome‐associated diseases and conditions. This research was supported from Whistler Center for Carbohydrate Research and USDA/AFRI.

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

“…Perhaps the high digestive activity of Ct-MGAM and Ct-SI on ␣-LDx is due to their ability to effectively cleave ␣-1,4-linkages close to the branch points, which is different from ␣-amylase. Related to the high hydrolytic activity of the C-terminal subunits, we recently showed that their selective inhibition with acarbose is an approach to slow glucogenesis of ␣-LDx (13).…”

Cyanidin-3-O-glucoside Ameliorates Postprandial Hyperglycemia in Diabetic Mice

“…One of the best ways to lower postprandial glucose levels in the context of hyperglycemia is to inhibit the entry of glucose into the intestinal endothelial cells by limiting the expression of carbohydrate-hydrolyzing enzymes such as mucosal glucosidases [19]. Intestinal α-glucosidase and pancreatic α-amylase are the major enzymes of dietary carbohydrate digestion in humans, and they hydrolyze inner α-1,4-glucosidic linkages in starch and several other polysaccharides [18].…”

Modeling of cooked starch digestion process using recombinant human pancreatic α-amylase and maltase-glucoamylase for in vitro evaluation of α-glucosidase inhibitors

“…8 In contrast, the membrane-bound ntMGAM subunit digests only linear oligomers at a relatively lower rate than ctMGAM (or the immunoprecipitated native MGAM complex from human intestinal mucosa). 12,15,35 In light of our IC 50 data on the various inhibitors on the in vitro cooked starch digestion process, acarviosine-containing pseudooligosaccharide inhibitors, including acarbose, AI03, AII03, AIII03 and AIV03, generally show higher inhibitory activities than pseudomonosaccharide inhibitors, including DNJ, miglitol and voglibose. Against individual recombinant enzymes, DNJ shows a strong inhibitory effect against ctMGAM, but no detectable inhibitory activity on HPA.…”

“…ctMGAM has higher affinity for longer maltose oligosaccharides compared to the ntMGAM. 15,16 Structural studies revealed major differences in the active sites between ctMGAM and ntMGAM. The active site of ctMGAM has an extra segment of 21 amino acids compared to the ntMGAM.…”