A suppressive role of c-kinase for the stimulation of hepatic ketogenesis by glucagon and epinephrine.
The regulatory mechanism of hepatic palmitate oxidation into ketone bodies by c-kinase has been studied in isolated hepatocytes. Glucagon and epinephrine stimulated [U-14C]palmitate oxidation to ketone bodies by 60 and 25% as early as at 1 h. The stimulatory effects were almost totally prevented by the simultaneous presence of vasopressin, phorbol 12-tetradecanoate 13-acetate (TPA), or diacylglycerol (1-oleoyl-2-acetylglycerol). When hepatocytes were treated with glucagon or epinephrine, carnitine palmitoyltransferase (CPT), a key regulatory enzyme of palmitate oxidation, was activated. This hormone-induced activation of CPT was not observed in the presence of TPA. These observations suggest that c-kinase inhibits glucagon- or epinephrine-stimulated palmitate oxidation to ketone bodies, and that this inhibition may be mediated through a covalent modification of CPT.
H
H
Kojima
Y
Y
Harano
K
K
Kosugi
T
T
Nakano
Y
Y
Shigeta
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D004075:Diglycerides; D007657:Ketone Bodies; D010169:Palmitic Acids; D014667:Vasopressins; D019308:Palmitic Acid; C038237:1-oleoyl-2-acetylglycerol; D005934:Glucagon; D002334:Carnitine O-Palmitoyltransferase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine