Direct activating effects of dexamethasone on glycogen metabolizing enzymes in primary cultured rat hepatocytes.
The direct effects of dexamethasone on glycogen synthase and phosphorylase and glycogen content have been investigated in primary cultured rat hepatocytes. Dexamethasone induced the transient translocation of glycogen synthase from the soluble to the 10000xg pelletable fraction and the activation of this enzyme, although more significant, longer-standing activation was achieved in the pelletable fraction. Neither total glycogen synthase content nor glycogen synthase mRNA levels were modified. Dexamethasone also caused the sustained activation (up to 6h) of glycogen phosphorylase, which was not accompanied by an increase in its mRNA level. Glycogen cell content and the incorporation of (14C) glucose into glycogen decreased after dexamethasone treatment. The data show that dexamethasone, unlike other glycogenolytic hormones, at concentrations of 10 nM or higher, stimulate hepatocyte glycogenolysis without inducing the inverse coupling of synthase and phosphorylase. The co-existence of active forms of both glycogen synthase and phosphorylase promoted by dexamethasone leads to a situation that is analogous to that of the fasted liver.
Baqué
S
S
Department of Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Spain.
Roca
A
A
Guinovart
J J
JJ
Gómez-Foix
A M
AM
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008112:Liver Glycogen / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D010762:Phosphorylase a / Q000378:metabolism; D006005:Phosphorylases / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D008112:Liver Glycogen; D012333:RNA, Messenger; D003907:Dexamethasone; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D005947:Glucose