Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes
Open Access
- 1 February 2000
- journal article
- research article
- Published by Wolters Kluwer Health in Hepatology
- Vol. 31 (2), 461-468
- https://doi.org/10.1002/hep.510310228
Abstract
The participation of phosphatidylinositol 3-kinase (PI3-kinase), protein kinase C, and mitogen-activated protein kinase (MAP-kinase) in the inhibition by interleukin 6 (IL-6) and insulin of phosphoenolpyruvate carboxykinase (PCK) gene expression was investigated in cultured rat hepatocytes. IL-6 or insulin inhibited the glucagon-stimulated increase in PCK messenger RNA (mRNA) by about 70%. In the presence of either the PI3-kinase inhibitor, wortmannin, or the protein kinase C inhibitor, GF109203x, the inhibition by IL-6 was only about 40%, although it was abolished with both inhibitors in combination. Wortmannin alone but not GF109203x prevented the inhibition by insulin of glucagon-stimulated PCK gene expression. The MAP-kinase pathway inhibitor, PD98059, did not affect IL-6 or insulin inhibition of PCK mRNA increase. When chlorophenylthio-cyclic 3′,5′ adenosine monophosphate (CPT-cAMP) was used instead of glucagon, IL-6 or insulin inhibited the increase in PCK mRNA by 75% and 85%, respectively. The inhibition by IL-6 was only about 50% in the presence of either wortmannin or GF109203x alone but was abolished with the combination of both inhibitors. The inhibition by insulin was only about 50% in the presence of GF109203x and was abolished by wortmannin. The inhibitors did not affect the inhibition by IL-6 or insulin of the glucagon-stimulated increase in cAMP. It is concluded that the inhibition by IL-6 of PCK gene expression involved both PI3-kinase and protein kinase C, whereas the inhibition by insulin required only PI3-kinase. The inhibition occurred downstream from cAMP formation. Hence, IL-6 and insulin may share, in part, common signal transduction pathways in the inhibition of PCK gene expression.Keywords
This publication has 42 references indexed in Scilit:
- Bidirectional modulation of insulin action by amino acids.JCI Insight, 1998
- Activation of the Ras Mitogen-activated Protein Kinase-Ribosomal Protein Kinase Pathway Is Not Required for the Repression of Phosphoenolpyruvate Carboxykinase Gene Transcription by InsulinPublished by Elsevier ,1998
- Insulin Regulation of Phosphoenolpyruvate Carboxykinase Gene Expression Does Not Require Activation of the Ras/Mitogen-activated Protein Kinase Signaling PathwayPublished by Elsevier ,1996
- Requirement of Serine Phosphorylation for Formation of STAT-Promoter ComplexesScience, 1995
- Interleukin‐6‐induced serine phosphorylation of transcription factor APRF: evidence for a role in interleukin‐6 target gene inductionFEBS Letters, 1995
- Alterations in carbohydrate metabolism during stress: A review of the literatureThe American Journal of Medicine, 1995
- Inhibition by PGE2 of glucagon‐induced increase in phosphoenolpyruvate carboxykinase mRNA and acceleration of mRNA degradation in cultured rat hepatocytesFEBS Letters, 1994
- Mechanism of the Inhibition by Insulin of the Glucagon-Dependent Activation of the Phosphoenolpyruvate Carhoxykinase Gene in Rat Hepatocyte Cultures. Action on Gene Transcription, mRNA Level and -Stability as well as Hysteresis EffectBiological Chemistry Hoppe-Seyler, 1990
- Predominant localization of phosphoenolpyruvate carboxykinase mRNA in the periportal zone of rat liver parenchyma demonstrated by in situ hybridizationFEBS Letters, 1989
- Regulation of the expression of the phosphoenolpyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulinEuropean Journal of Biochemistry, 1988