Inhibition by PGE2 of glucagon-induced increase in phosphoenolpyruvate carboxykinase mRNA and acceleration of mRNA degradation in cultured rat hepatocytes.
In cultured rat hepatocytes the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK) is known to be induced by glucagon via an elevation of cAMP. Prostaglandin E2 has been shown to antagonize the glucagon-activated cAMP formation, glycogen phosphorylase activity and glucose output in hepatocytes. It was the purpose of the current investigation to study the potential of PGE2 to inhibit the glucagon-induced expression of PCK on the level of mRNA and enzyme activity. PCK mRNA and enzyme activity were increased by 0.1 nM glucagon to a maximum after 2 h and 4 h, respectively. This increase was completely inhibited if 10 microM PGE2 was added concomitantly with glucagon. This inhibition by PGE2 of glucagon-induced PCK activity was abolished by pertussis toxin treatment. When added at the maximum of PCK mRNA at 2 h, PGE2 accelerated the decay of mRNA and reduced enzyme activity. This effect was not reversed by pertussis toxin treatment. Since in liver PGE2 is derived from Kupffer cells, which play a key role in the local inflammatory response, the present data imply that during inflammation PGE2 may reduce the hepatic gluconeogenic capacity via a Gi-linked signal chain.
Püschel
G P
GP
Institut für Biochemie und Molekulare Zellbiologie, Georg-August-Universität, Göttingen, Germany.
Christ
B
B
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D037342:Pertussis Toxin; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D005934:Glucagon; D037342:Pertussis Toxin; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D015232:Dinoprostone