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

Ngo, Sherry, Barry, Janelle B., Nisbet, Janelle C., Prins, Johannes B. and Whitehead, Jonathan P. (2009) Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes. Molecular and Cellular Endocrinology, 302 1: 33-40. doi:10.1016/j.mce.2008.10.020


Author Ngo, Sherry
Barry, Janelle B.
Nisbet, Janelle C.
Prins, Johannes B.
Whitehead, Jonathan P.
Title Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes
Journal name Molecular and Cellular Endocrinology   Check publisher's open access policy
ISSN 0303-7207
Publication date 2009-04-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.mce.2008.10.020
Open Access Status
Volume 302
Issue 1
Start page 33
End page 40
Total pages 8
Place of publication Ireland
Publisher Elsevier Ireland Ltd
Language eng
Subject C1
920106 Endocrine Organs and Diseases (excl. Diabetes)
060104 Cell Metabolism
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.
Keyword AS160
GLUT
Adipocyte
Glucose transport
Glucocorticoid
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 31 Mar 2009, 23:33:58 EST by Kylie Hengst on behalf of UQ Diamantina Institute