Insulin inhibition of glucose-6-phosphatase gene expression is dependent on the phosphatidylinositol-3-kinase(pi-3-k) pathway, not the ras/map kinase pathway

Sei-Hyun Baik, K. Trinh, I. Garcia, K. Nguyen, I. J. Kurland

Research output: Contribution to journalArticle

Abstract

Glucose-6-phosphatase(G6Pase) is a key enzyme of hepatic gluconeogenesis. The expression of this gene is well known to be inhibited by insulin. but the pathway by which insulin influences this inhibition is not known. Insulin activates a signahng cascade involving the stimulation of insulin receptor tyrosine kinase activity, tyrosine phosphorylation of insulin receptor substrates(IRS-1/2), RasRaf-+p42/p44 Mitogen activated protein(MAP) kinase kinase(MEK)p42/p44 MAP kinase. The sociation of the p85 subunit of PI-3-K with IRS-1/2 confers an increase in the activity of the pl].0 catalytic subunit of PI-3-K which activates Akt/Rac and p70 6 kinase (pT0 S6K). The aim of this study was to evaluate the roles of insulin stimulated Ras/MAP ki nase versus PI-3-K pathways in regulation of G6Pase gene expression in FAO hepatoma cells. The effect of insulin to inhibit G6Pase gene expression was antagonized by the presence of 200 nanomolar (nM) wortmannin(PI-3-K inhibitor) for insulin concentrations ranging from 0.1 to 10 nM. There was no antagonism of insulin's inhibitory effects on G6Pase gene expression by t0 micromolar PD98059(MEK inhibitor), or 100 nM rapamycin (pT0 S6K inhibitor), either alone or in combination. We conclude that PI-3-K pathway has a crucial role in mediating insulin's effect to inhibit G6Pase gene expression.

Original languageEnglish
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - 1997 Dec 1

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Phosphatidylinositol 3-Kinase
Glucose-6-Phosphatase
Gene expression
Phosphotransferases
Insulin
Gene Expression
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Insulin Receptor Substrate Proteins
Phosphorylation
Gluconeogenesis
Insulin Receptor
Sirolimus
Mitogen-Activated Protein Kinases
Mitogens
Tyrosine
Hepatocellular Carcinoma
Catalytic Domain
Genes
Liver

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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Insulin inhibition of glucose-6-phosphatase gene expression is dependent on the phosphatidylinositol-3-kinase(pi-3-k) pathway, not the ras/map kinase pathway. / Baik, Sei-Hyun; Trinh, K.; Garcia, I.; Nguyen, K.; Kurland, I. J.

In: FASEB Journal, Vol. 11, No. 9, 01.12.1997.

Research output: Contribution to journalArticle

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