Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes

Christ, Bruno; Yazıcı, Emine Şule; Nath, Annegret

doi:10.1002/hep.510310228

Cited by 21 publications

(15 citation statements)

References 45 publications

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“…IL6st forms homo- and heterodimers with other signal transducing subunits in response to binding by an assortment of ligands including IL-6, IL-11, LIF, CT-1, CNTF, and OSM [55]. Among these, IL-6 knockout mice develop mature-onset obesity [56], and treatment of hepatocytes with IL-6 reduces the expression of PCK1 [6], thus implicating IL-6 in the regulation of hepatic glucose output. There are at least four different Jaks (Jak1, Jak2, Jak3, and Tyk2) and seven different STAT factors (STAT1, 2, 3, 4, 5a, 5b, and 6) that can interact with IL6st.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction

et al. 2005

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Background: Obesity is associated with insulin resistance that can often be improved by caloric restriction and weight reduction. Although many physiological changes accompanying insulin resistance and its treatment have been characterized, the genetic mechanisms linking obesity to insulin resistance are largely unknown. We used DNA microarrys and RT-PCR to investigate significant changes in hepatic gene transcription in insulin resistant, diet-induced obese (DIO)-C57/BL/6J mice and DIO-C57/BL/6J mice fasted for 48 hours, whose weights returned to baseline levels during these conditions.

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Section: Discussionmentioning

confidence: 99%

“…In the liver, hepatic glucose output (HGO) increases during insulin resistance and several key molecules contributing to this phenotype have been widely studied [3-6]. Despite these extensive efforts, the genes identified thus far do not alone account for all of the variability in HGO.…”

Section: Introductionmentioning

confidence: 99%

Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction

et al. 2005

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“…Studies in cultured rat hepatocytes and in rat hepatoma cells showed that stimulation of the expression of the rat PCK gene by glucagon or cAMP was inhibited by insulin through the PI 3- kinase pathway [27][28][29][30]. The luciferase expression vector controlled by the human promoter was transfected into rat hepatocytes to investigate whether PI 3-kinase was also required for the insulin inhibition of the human PCK gene promoter.…”

Section: Involvement Of Phosphoinositide 3-kinase ( Pi 3-kinase) In Imentioning

confidence: 99%

Regulation by glucagon (cAMP) and insulin of the promoter of the human phosphoenolpyruvate carboxykinase gene (cytosolic) in cultured rat hepatocytes and in human hepatoblastoma cells

2000

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A promoter fragment (-457 to +65) of the human cytosolic phosphoenolpyruvate carboxykinase gene, which by analogy to the rat promoter contains regulatory regions conferring glucagon (cAMP) and insulin responsiveness to the phosphoenolpyruvate carboxykinase gene, was cloned into a luciferase expression vector and transfected into cultured rat hepatocytes and human hepatoblastoma cells (HepG2) to study the regulation of the transgene by glucagon (cAMP) and insulin. A reporter gene that contained the rat promoter sequence from -493 to +33 was used for comparison. In cultured rat hepatocytes glucagon and its second messenger cAMP increased luciferase expression 4-6-fold over basal levels. Insulin reduced this effect by 40-70%. Luciferase expression was also stimulated by the combination of dexamethasone and cAMP in HepG2 cells and this effect was inhibited by insulin. The phosphoinositide 3-kinase (PI 3-kinase) inhibitor, wortmannin, abolished this action of insulin in cultured rat hepatocytes. The results show that the promoter of the human phosphoenolpyruvate carboxykinase gene mediates the stimulatory action of glucagon and its second messenger cAMP. The inhibitory action of insulin was exerted through the PI 3-kinase pathway in cultured rat hepatocytes.

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“…1). Huh-7 or HepG2 cells were treated with 100 nM of PMA (Roman et al, 1998), 50 nM of okadaic acid (Taylor et al, 1999) or 250 nM of wortmannin (Christ et al, 2000) in the absence or presence of 10 mM heme (Cable et al, 2000). The concentrations chosen were shown to be effective in hepatocytes or hepatic cell lines.…”

Section: Effects Of Kinase or Phosphatase Modulators On Ala Synthase mentioning

confidence: 99%

Effects of Modulators of Protein Phosphorylation on Heme Metabolism in Human Hepatic Cells: Induction ofδ-Aminolevulinic Synthase mRNA and Protein by Okadaic Acid

Cable

Kühn

Isom

2002

DNA and Cell Biology

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Effects of modulators of protein phosphorylation on delta-aminolevulinic acid (ALA) synthase and heme oxygenase-1 mRNA were analyzed in the human hepatic cell lines Huh-7 and HepG2 using a quantitative RNase protection assay. Okadaic acid was found to induce ALA synthase mRNA in a concentration-dependent fashion in both Huh-7 and HepG2 cells. The EC(50) for induction of ALA synthase mRNA in Huh-7 cells was 13.5 nM, with maximum increases occurring at okadaic acid concentrations of 25-50 nM. The EC(50) for induction of ALA synthase mRNA in HepG2 cells was 35.5 nM, with maximum increases occurring at okadaic acid concentrations of 50 nM. Concentration-dependent induction of ALA synthase mRNA paralleled the increase in ALA synthase protein. Maximum induction of ALA synthase was observed between 5 and 10 h post-treatment in both cell lines. Induction of ALA synthase mRNA in Huh-7 cells, but not HepG2 cells, was associated with an increase in ALA synthase mRNA stability. Okadaic acid also induced heme oxygenase-1 mRNA in both cell lines, but the magnitude of induction was only twofold, and was rapid and transient. Okadaic acid and phorbol 12-myristate 13-acetate significantly decreased heme-mediated induction of heme oxygenase-1 mRNA in both Huh-7 and HepG2 cells. Wortmannin diminished the heme-mediated induction of heme oxygenase-1 mRNA in HepG2 cells, but not Huh-7 cells. These results report a novel property of okadaic acid to affect heme metabolism in human cell lines.

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Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes

Cited by 21 publications

References 45 publications

Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction

Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction

Regulation by glucagon (cAMP) and insulin of the promoter of the human phosphoenolpyruvate carboxykinase gene (cytosolic) in cultured rat hepatocytes and in human hepatoblastoma cells

Effects of Modulators of Protein Phosphorylation on Heme Metabolism in Human Hepatic Cells: Induction ofδ-Aminolevulinic Synthase mRNA and Protein by Okadaic Acid

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