title: Miglustat-induced intestinal carbohydrate malabsorption is due to the inhibition of α-glucosidases, but not β-galactosidases.
abstract: Miglustat is an oral medication that has approved indication for type I Gaucher disease and Niemann pick disease type C. Usually treatment with Miglustat is associated with occurrence of gastrointestinal side effects similar to carbohydrate maldigestion symptoms. Here, we studied the direct influence of Miglustat on the enzymatic function of the major disaccharidases of the intestinal epithelium. Our findings show that an immediate effect of Miglustat is its interference with carbohydrate digestion in the intestinal lumen via reversible inhibition of disaccharidases that cleave α-glycosidically linked carbohydrates. Higher non physiological concentrations of Miglustat can partly affect lactase activity. We further show that the inhibition of the disaccharidases function by Miglustat is mainly competitive and does not occur via alteration of the enzyme folding.
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hannover, Germany.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Amiri
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004040:Dietary Carbohydrates / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005776:Gaucher Disease / Q000188:drug therapy; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D008286:Malabsorption Syndromes / Q000139:chemically induced* / Q000201:enzymology*; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors*
chemical_list: D004040:Dietary Carbohydrates; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat; D001616:beta-Galactosidase