Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes
Sherry Ngo, Janelle B Barry, Janelle C Nisbet, Johannes B Prins, Jonathan P Whitehead
MOLECULAR AND CELLULAR ENDOCRINOLOGY | ELSEVIER IRELAND LTD | Published : 2009
Excess glucocorticoids induce insulin resistance and reduce glucose uptake although the underlying mechanisms are unclear. Here we demonstrate that Dex (1 microM for 24h) 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 160kDa (AS160) at T642, which is essential for 14-3-3 recruitment and GLUT4 translocation, was reduced by 50% in ba..View full abstract
This work was funded by the NHMRC, the Diabetes Australia Research Trust, the Lions Medical Research Foundation and the Princess Alexandra Hospital Foundation.