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      Regulation of the absorption of dietary carbohydrate in man by two new glycosidase inhibitors.

      Gut

      analogs & derivatives, Adult, Blood Glucose, metabolism, Dietary Carbohydrates, Dose-Response Relationship, Drug, Glucosamine, pharmacology, Glycoside Hydrolases, antagonists & inhibitors, Humans, Hydrogen, Imino Pyranoses, Intestinal Absorption, drug effects, Male, Maltose, Starch, Substrate Specificity, Sucrose, 1-Deoxynojirimycin

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          Abstract

          Two new reversible inhibitors of intestinal alpha-glycosidases (BAY m1099 & o1248) have been derived from deoxynojirimycin. Their inhibitory substrate specificity has been investigated in man using test meals of the dietary carbohydrates, sucrose, maltose, and starch. Both inhibitors abolished the postprandial glycaemic rise after sucrose and m1099 50 mg did after maltose and starch, whereas o1248 20 mg had no effect after maltose and only a small effect after starch. Breath hydrogen evolution, as an indirect measure of malabsorption, showed that the reduced glycaemic responses, particularly after sucrose, were associated with considerable substrate malabsorption. Dose response studies showed that lower doses of both inhibitors could reduce postprandial glycaemia significantly without causing malabsorption. Both inhibitors were tolerated well. These two new enzyme inhibitors have different substrate specificity in man and can, in appropriate dose, regulate postprandial glycaemia by selective inhibition of brush border enzymes without causing malabsorption. In addition to their therapeutic importance, they provide a valuable experimental model of specific intestinal enzyme deficiency states.

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          Journal
          3804023
          1433974

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