Regulation oftheabsorption ofdietary carbohydrate inman bytwonew glycosidase inhibitors

SUMMARY Two new reversible inhibitors ofintestinal a-glycosidases (BAYmlO99& o1248) havebeenderived fromdeoxynoj irimycin. Theirinhibitory substrate specificity hasbeen investigated inman using testmealsofthedietary carbohydrates, sucrose,maltose, andstarch. Bothinhibitors abolished thepostprandial glycaemic riseafter sucroseandmlO9950mg didafter maltose andstarch, whereas o124820mg hadno effect after maltose andonly asmall effect after starch. Breath hydrogen evolution, as an indirect measure ofmalabsorption, showedthatthe reduced glycaemic responses,particularly after sucrose,were associated withconsiderable substrate malabsorption. Doseresponsestudies showedthatlowerdoses ofbothinhibitors could reduce postprandial glycaemia significantly without causing malabsorption. Bothinhibitors were tolerated well. Thesetwonew enzyme inhibitors havedifferent substrate specificity inman and can,inappropriate dose, regulate postprandial glycaemia byselective inhibition ofbrushborder enzymes without causingmalabsorption. Inaddition totheirtherapeutic importance, they provide a valuable experimental modelofspecific intestinal enzyme deficiency states.