Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2002, PMID: 11784721

Insulin regulation of insulin-like growth factor-binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity.

Patel, Satish; Lochhead, Pamela A; Rena, Graham; Fumagalli, Stefano; Pende, Mario; Kozma, Sara C; Thomas, George; Sutherland, Calum

Insulin inhibits the expression of the hepatic insulin-like growth factor-binding protein-1 (IGFBP-1) and glucose-6-phosphatase (G6Pase) genes. The signaling pathway that mediates these events requires the activation of phosphatidylinositol 3-kinase, whereas transfection studies have suggested an involvement of Akt (protein kinase B) and FKHR, a transcription factor regulated by Akt. We now demonstrate that insulin repression of endogenous IGFBP-1 gene transcription was blocked by rapamycin or by amino acid starvation. Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin, whereas amino acid depletion prevented insulin induction of these signaling molecules. Importantly, we demonstrate that insulin regulation of the thymine-rich insulin response element of the IGFBP-1 promoter was also inhibited by rapamycin. However, sustained activation of S6K1 did not repress this promoter. In addition, rapamycin did not affect insulin regulation of G6Pase expression or Akt activation. We propose that these observations indicate that an mTOR-dependent, but S6K-independent mechanism regulates the suppression of IGFBP-1 (but not G6Pase) gene expression by insulin. Therefore, although the insulin-responsive sequence of the G6Pase gene promoter is related to that of the IGFBP-1 promoter, the signaling pathways that mediate suppression of these genes are distinct.

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Text Mining Data

insulin-like growth factor ⊣ mammalian target of rapamycin: " Insulin regulation of insulin-like growth factor binding protein-1 gene expression is dependent on the mammalian target of rapamycin , but independent of ribosomal S6 kinase activity "

Insulin → mammalian target of rapamycin: " Insulin regulation of insulin-like growth factor binding protein-1 gene expression is dependent on the mammalian target of rapamycin , but independent of ribosomal S6 kinase activity "

insulin-like growth factor — Insulin: " Insulin regulation of insulin-like growth factor binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity "

glucose-6-phosphatase (G6Pase) ⊣ Insulin: " Insulin inhibits the expression of the hepatic insulin-like growth factor binding protein-1 ( IGFBP-1 ) and glucose-6-phosphatase (G6Pase) genes "

IGFBP-1 ⊣ Insulin: " Insulin inhibits the expression of the hepatic insulin-like growth factor binding protein-1 ( IGFBP-1 ) and glucose-6-phosphatase (G6Pase) genes "

transcription factor — Akt: " The signaling pathway that mediates these events requires the activation of phosphatidylinositol 3-kinase, whereas transfection studies have suggested an involvement of Akt ( protein kinase B ) and FKHR, a transcription factor regulated by Akt "

S6 protein kinase-1 (S6K1) → insulin: " Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin , whereas amino acid depletion prevented insulin induction of these signaling molecules "

mammalian target of rapamycin (mTOR) → S6 protein kinase-1 (S6K1): " Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin, whereas amino acid depletion prevented insulin induction of these signaling molecules "

mammalian target of rapamycin (mTOR) → insulin: " Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin , whereas amino acid depletion prevented insulin induction of these signaling molecules "

Akt → G6Pase: " In addition, rapamycin did not affect insulin regulation of G6Pase expression or Akt activation "

G6Pase — insulin: " In addition, rapamycin did not affect insulin regulation of G6Pase expression or Akt activation "

IGFBP-1 ⊣ mTOR: " We propose that these observations indicate that an mTOR dependent, but S6K independent mechanism regulates the suppression of IGFBP-1 ( but not G6Pase ) gene expression by insulin "

Manually curated Databases

No curated data.