dc.contributor.author | Finlay, David | en |
dc.date.accessioned | 2011-11-02T11:19:44Z | |
dc.date.available | 2011-11-02T11:19:44Z | |
dc.date.issued | 2006 | en |
dc.date.submitted | 2006 | en |
dc.identifier.citation | Finlay D., Ruiz-Alcaraz AJ., Lipina C., Perrier S., Sutherland C, A temporal switch in the insulin-signalling pathway that regulates hepatic IGF-binding protein-1 gene expression, Journal of Molecular Endocrinology, 37, 2, 2006, 227 - 237 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/60439 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Insulin regulation of hepatic gene transcription is a vital component of glucose homeostasis. Understanding the molecular regulationof thisprocess aids the searchfor the defect(s) that promotesinsulin-resistant states, such asdiabetesmellitus. We havepreviously shownthat the insulin regulationof hepatic IGF-binding protein-1 (IGFBP1) expression requiresthe signalling proteins phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamycin (mTOR). In this report, we demonstrate that activation of the mTOR pathway, without activation of its upstream regulator PI 3-kinase, reduces IGFBP1 expression. Therefore, mTOR activation is sufficient to mimic insulin regulation of this gene. However, longer exposure (>3 h) of cells to insulin reduces the importance of this pathway in insulin regulation of the gene, suggesting a temporal switch in signalling mechanisms linking insulin action to the IGFBP1 gene promoter. In contrast, the activation of PI 3-kinase is required for insulin regulation of IGFBP1 under all conditions tested. Therefore, an mTOR-independent, PI 3-kinase-dependent pathway becomes more important in IGFBP1 regulation after long exposure to insulin. This is a novel concept in insulin regulation of gene expression and demonstrates the importance of temporal analysis of signalling processes. | en |
dc.format.extent | 227 | en |
dc.format.extent | 237 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Journal of Molecular Endocrinology | en |
dc.relation.ispartofseries | 37 | en |
dc.relation.ispartofseries | 2 | en |
dc.rights | Y | en |
dc.subject | Genetics | en |
dc.subject | Insulin | en |
dc.title | A temporal switch in the insulin-signalling pathway that regulates hepatic IGF-binding protein-1 gene expression | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/finlayd | en |
dc.identifier.rssinternalid | 75190 | en |
dc.identifier.rssuri | http://dx.doi.org/10.1677/jme.1.02084 | en |
dc.identifier.orcid_id | 0000-0003-2716-6679 | en |