1-Deoxynojirimycin and related compounds inhibit glycogenolysis in the liver without affecting the concentration of phosphorylase a.
Administration in vivo of the alpha-glucosidase inhibitors 1-deoxynojirimycin and its derivatives BAY m 1099 (miglitol) and BAY o 1248 resulted in a dose- and time-dependent decrease in the rate of hepatic glycogenolysis induced by glucagon. This represents a direct effect on the liver, since it could be reproduced on isolated hepatocytes. The amount of glucose produced by hepatocytes over a period of 10-20 min after addition of glucagon was decreased by about 70, 60 and 45% in the presence of maximally effective concentrations of BAY o 1248, deoxynojirimycin, and BAY m 1099, respectively. Half-maximal effects were observed at inhibitor concentrations between 20 and 100 microM. The concentrations of phosphorylase a and glycogen synthase a were not affected by inclusion of the alpha-glucosidase inhibitors in the hepatocyte suspensions. Thus, the antiglycogenolytic action of these compounds is not mediated by an altered activation state of the rate-limiting enzymes of glycogenolysis and of glycogen synthesis.
Bollen
M
M
Afdeling Biochemie, Fakulteit Geneeskunde, Katholieke Universiteit Leuven, Belgium.
Vandebroeck
A
A
Stalmans
W
W
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D008099:Liver / Q000201:enzymology*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010762:Phosphorylase a / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D008112:Liver Glycogen; C045621:miglitol; D017485:1-Deoxynojirimycin; D005934:Glucagon; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D005944:Glucosamine