title: Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal α-glucosidases.
abstract: Starch digestion involves the breakdown by α-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal α-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 α-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit has an additional exo-debranching activity on the α-1,6-linkage. Inhibition of α-amylase and/or α-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 α-amylolyzed starch malto-oligosaccharides with the aim of slow glucose delivery. Recombinant MGAM and SI subunits were individually assayed with α-amylolyzed waxy corn starch, consisting mainly of maltose, maltotriose, and branched α-limit dextrins, as substrate in the presence of four different inhibitors: acarbose and three sulfonium ion compounds. The IC(50) values show that the four α-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 α-glucosidases by selective enzyme inhibition. This approach could also be used to probe associated metabolic diseases.
authors.affiliation: Department of Food Science, Whistler Center for Carbohydrate Research, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Byung-Hoo
authors.initials: BH
authors.lastname: Lee
authors.forename: Razieh
authors.initials: R
authors.lastname: Eskandari
authors.forename: Kyra
authors.initials: K
authors.lastname: Jones
authors.forename: Kongara Ravinder
authors.initials: KR
authors.lastname: Reddy
authors.forename: Roberto
authors.initials: R
authors.lastname: Quezada-Calvillo
authors.forename: Buford L
authors.initials: BL
authors.lastname: Nichols
authors.forename: David R
authors.initials: DR
authors.lastname: Rose
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Hamaker
authors.forename: B Mario
authors.initials: BM
authors.lastname: Pinto
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism; D004331:Drosophila melanogaster; D005947:Glucose / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D009092:Mucous Membrane / Q000201:enzymology*; D009765:Obesity / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D006026:Glycoside Hydrolases; D000520:alpha-Glucosidases; D005947:Glucose