Metabolic effects of proglycosyn.
Proglycosyn, a phenylacyl imidazolium compound that lowers blood glucose levels, was demonstrated previously to promote hepatic glycogen synthesis, stabilize hepatic glycogen stores, activate glycogen synthase, inactivate glycogen phosphorylase, and inhibit glycolysis. In the present study proglycosyn was found to inhibit fatty acid synthesis, stimulate fatty acid oxidation, and lower fructose 2,6-bisphosphate levels, but to have no significant effects on cell swelling and the levels of cAMP in hepatocytes prepared from fed rats. Verapamil and atropine blocked the effects of proglycosyn on glycogen metabolism, but these compounds inhibit proglycosyn accumulation by hepatocytes. Proglycosyn stimulated phosphoprotein phosphatase activity in postmitochondrial extracts, as measured by dephosphorylation of phosphorylase a and glycogen synthase D, but this action required a very high concentration of the compound, making it unlikely to be the actual mechanism involved. It is proposed that a metabolite of proglycosyn is responsible for its metabolic effects.
Yamanouchi
K
K
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202-5122.
Stephens
T W
TW
Chikada
K
K
Dominianni
S J
SJ
Behforouz
H
H
Scislowski
P
P
DePaoli-Roach
A
A
Allmann
D W
DW
Harris
R A
RA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007093:Imidazoles; D008112:Liver Glycogen; C060944:proglycosyn; D015124:8-Bromo Cyclic Adenosine Monophosphate; D001285:Atropine; D005934:Glucagon; D014700:Verapamil; D000242:Cyclic AMP; D010762:Phosphorylase a; D006006:Glycogen Synthase; D010749:Phosphoprotein Phosphatases