Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes

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dc.contributor.author Ngo, Sherry en
dc.contributor.author Barry, J en
dc.contributor.author Nisbet, JC en
dc.contributor.author Prins, JB en
dc.contributor.author Whitehead, JP en
dc.date.accessioned 2012-05-27T08:01:40Z en
dc.date.issued 2009-04 en
dc.identifier.citation Molecular and Cellular Endocrinology 302(1):33-40 Apr 2009 en
dc.identifier.issn 0303-7207 en
dc.identifier.uri http://hdl.handle.net/2292/18464 en
dc.description.abstract Excess glucocorticoids induce insulin resistance and reduce glucose uptake although the underlying mechanisms are unclear. Here we demonstrate that Dex (1 μM for 24 h) inhibits basal and insulin (1 nM) stimulated glucose uptake in human and murine adipocytes by 50% with a concomitant reduction in the levels of GLUT1/4 at the plasma membrane but no change in total GLUT1/4 levels. Expression and phosphorylation of proximal insulin signalling molecules (IRS1, PI3K, AKT) was unaffected by Dex as was phosphorylation of mTOR and FOXO1. In contrast, phosphorylation of AKT substrate 160 kDa (AS160) at T642, which is essential for 14-3-3 recruitment and GLUT4 translocation, was reduced by 50% in basal and insulin-stimulated cells and this was mirrored by decreased 14-3-3 association. Co-treatment with the glucocorticoid receptor antagonist RU486 (10 μM) abrogated the Dex effect on AS160-T642 phosphorylation and restored glucose uptake by 80%. These data suggest Dex inhibits glucose uptake in adipocytes, at least in part, by reducing AS160 phosphorylation and interaction with 14-3-3. en
dc.publisher Elsevier Ireland Ltd. en
dc.relation.ispartofseries Molecular and Cellular Endocrinology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0303-7207/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.mce.2008.10.020 en
pubs.issue 1 en
pubs.begin-page 33 en
pubs.volume 302 en
dc.rights.holder Copyright: IEEE en
pubs.end-page 40 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 100118 en
pubs.record-created-at-source-date 2010-09-01 en


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