Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal α-glucosidases

J Biol Chem. 2012 Sep 14;287(38):31929-38. doi: 10.1074/jbc.M112.351858. Epub 2012 Jul 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus / metabolism
  • Drosophila melanogaster
  • Glucose / metabolism*
  • Glycoside Hydrolases / chemistry
  • Glycosylation
  • Humans
  • Hydrolysis
  • Inhibitory Concentration 50
  • Intestinal Mucosa / metabolism
  • Kinetics
  • Mice
  • Models, Chemical
  • Mucous Membrane / enzymology*
  • Obesity / metabolism
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • alpha-Glucosidases / metabolism*

Substances

  • Recombinant Proteins
  • Glycoside Hydrolases
  • alpha-Glucosidases
  • Glucose