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Title: Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal "alpha"-glucosidases

item LEE, BYUNG-HOO - Purdue University
item ESKANDARI, RAZIEH - Simon Fraser University
item JONES, KYRA - University Of Waterloo
item REDDY, KONGARA - Simon Fraser University
item QUEZADA-CALVILLO, ROBERTO - Centro De Investigacion
item NICHOLS, BUFORD - Children'S Nutrition Research Center (CNRC)
item ROSE, DAVID - University Of Waterloo
item HAMAKER, BRUCE - Purdue University
item PINTO, B. MARIO - Simon Fraser University

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/28/2012
Publication Date: 7/31/2012
Citation: Lee, B., Eskandari, R., Jones, K., Reddy, K.R., Quezada-Calvillo, R., Nichols, B.L., Rose, D.R., Hamaker, B.R., Pinto, B. 2012. Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal "alpha"-glucosidases. Journal of Biological Chemistry. 287(38):31929-31938.

Interpretive Summary: Starch food products are normally digested to glucose by enzymes in the small intestine. Different enzymes exist that break the starch into different sized pieces before eventually digesting these pieces into single glucose molecules. In this study, we looked at the possibility of inhibiting certain starch enzymes as a strategy for the prevention and treatment of type 2 diabetes or pre-diabetes. Starch enzymes were individually measured in the presence of different enzyme inhibitors for their ability to digest starch pieces into glucose. For each of the enzymes, specific inhibitors were identified that could impair the release of glucose from starch. These results suggest that the digestion of dietary starch could be controlled by the selective use of inhibitors, thereby helping to regulate type 2 diabetes or pre-diabetes.

Technical Abstract: 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 IC(50) 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.