Summary
The effect of a new complex oligosaccharide (Bay g 5421) of microbial origin on human intestinalα-glucosidehydrolase activity was tested in mucosal homogenate from human small bowel biopsy specimens.
Theα-glucosidehydrolase inhibitor (α-GHI) exerted a potent inhibitory effect on glucoamylase, sucrase, and maltase, was minimally effective on isomaltase, and did not affect trehalase and lactase activity. Kinetic analysis revealed a fully competitive type of inhibition with a Ki of 1.3 × 10−6M; thus the inhibitor had a 15 000-fold higher affinity to the enzyme sucrase than its natural substrate sucrose. The new compound may prove to be useful in the study of carbohydrate maldigestion and malabsorption and may possibly be of therapeutic benefit in diabetes and obesity.
Similar content being viewed by others
References
Alvarado, F., Crane, R. K.: Phlorizin as a competitive inhibitor of the active transport of sugars by hamster small intestine. Biochim. Biophys. Acta56, 170–180 (1962)
Caspary, W. F., Creutzfeldt, W.: Hemmung der intestinalen Resorption von Zuckern und Aminosäuren durch Prenylamin (Segontin®). Dtsch. Med. Wschr.97, 394–396 (1972)
Caspary, W. F.: Kohlenhydratresorption und Malabsorption. Leber Magen Darm7, 150–159 (1977a)
Caspary, W. F.: Mechanism and specificity of intestinal sugar transport. In: Intestinal Permeation, M. Kramer, F. Lauterbach (eds.), pp. 74–83. Amsterdam, Oxford: Excerpta Medica 1977b
Caspary, W. F.: Biguanides and intestinal absorptive function. Acta Hepato-Gastroenterol.24, 473–480 (1977c)
Crane, R. K., Menard, D., Preiser, H., Cerda, J.: The molecular basis of brush border membrane disease. In: Membranes and Diseases, L. Bolis, J. F. Hoffman, A. Leaf (eds.), pp. 229–241. New York: Raven Press 1976
Dahlqvist, A.: Method for assay of intestinal disaccharidases. Analyt. Biochem.7, 18–23 (1964)
Gottesbüren, H., Raida, H., Riecken, E. O.: Untersuchungen zum Einfluß von Prenylamin auf die Dünndarmresorption beim Menschen. Dtsch. Med. Wschr.99, 2104–2105 (1974)
Gray, G. M.: Carbohydrate digestion and absorption. New Engl. J. Med.292, 1225–1230 (1975)
Gray, G. M., Conklin, K. A., Townley, R. R. W.: Sucrase-isomaltase deficiency—absence of an inactive enzyme variant. New Engl. J. Med.294, 750–753 (1976)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem.193, 265–269 (1951)
Puls, W., Keup, U.: Influence of anα-amylase inhibitor on blood glucose, serum insulin and NEFA in starch loading tests in rats, dogs and man. Diabetologia9, 97–101 (1973)
Puls, W., Keup, U.: Inhibition of sucrase by TRIS in rats and man, demonstrated by oral loading tests with sucrose. Metabolism24, 93–98 (1975)
Puls, W., Keup, U., Krause, H. P., Thomas, G., Hoffmeister, F.: Glucosidase inhibition. A new approach to the treatment of diabetes, obesity and hyperlipoproteinemia. Naturwissenschaften64, 536 (1977)
Schmidt, D. D., Frommer, W., Junge, B., Müller, L., Wingender, W., Truscheit, E., Schäfer, D.:α-glucosidase inhibitors. New complex oligosaccharides of microbial origin. Naturwissenschaften64, 535 (1977)
Schmitz, J., Preiser, H., Maestracci, D., Ghosh, B. K., Cerda, J. J., Crane, R. K.: Purification of the human intestinal brush border membrane. Biochim. Biophys. Acta323, 98–105 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Caspary, W.F., Graf, S. Inhibition of human intestinalα-glucosidehydrolases by a new complex oligosaccharide. Res. Exp. Med. 175, 1–6 (1979). https://doi.org/10.1007/BF01851228
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01851228