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 μM 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.
| Identifer | oai:union.ndltd.org:Potsdam/oai:kobv.de-opus-ubp:4579 |
| Date | January 1994 |
| Creators | Püschel, Gerhard, Christ, Bruno |
| Publisher | Universität Potsdam, Mathematisch-Naturwissenschaftliche Fakultät. Institut für Ernährungswissenschaft |
| Source Sets | Potsdam University |
| Language | English |
| Detected Language | English |
| Type | Postprint |
| Format | application/pdf |
| Source | FEBS Letters 351 (1994), 3, p. 353-356, DOI 10.1016/0014-5793(94)00877-9, ISSN 0014-5793 |
| Rights | http://opus.kobv.de/ubp/doku/urheberrecht.php |
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