Effects of N-hydroxyethyl-1-deoxynojirimycin (BAY m 1099) on the activity of neutral- and acid alpha-glucosidases in human fibroblasts and HepG2 cells.
The effect of the glucose analogue N-hydroxyethyl-1-deoxynojirimycin (BAY m 1099) on the activity of alpha-glucosidases was studied in human fibroblasts and HepG2 cells. BAY m 1099 inhibits neutral and acid alpha-glucosidase activities of both cell types in a dosage-dependent and reversible manner. Inhibition of endoplasmic reticulum glucosidases I and/or II is suggested by delayed processing of lysosomal (acid) alpha-glucosidase. Competitive inhibition of mature acid alpha-glucosidase leads to lysosomal accumulation of glycogen as in glycogenosis type II. There seems to be little risk, however, of inducing this storage disorder when using the drug in a dose of 50 mg per os for treatment of type II diabetes. In high doses, the drug may prove useful for studying the pathogenesis of glycogenosis type II in vitro or in animal models.
Wisselaar
H A
HA
Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.
van Dongen
J M
JM
Reuser
A J
AJ
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000648:ultrastructure; D005347:Fibroblasts / Q000201:enzymology*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D050112:Imino Pyranoses; D007150:Immunohistochemistry; D007700:Kinetics; D008113:Liver Neoplasms / Q000201:enzymology* / Q000648:ultrastructure; D008247:Lysosomes / Q000201:enzymology; D008854:Microscopy, Electron; D008970:Molecular Weight; D014407:Tumor Cells, Cultured; D000520:alpha-Glucosidases / Q000096:biosynthesis
D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; C045621:miglitol; D017485:1-Deoxynojirimycin; D006003:Glycogen; D000520:alpha-Glucosidases; D005944:Glucosamine