DEXAMETHASONE STIMULATES THE EXPRESSION OF GLUT1 AND GLUT4 PROTEINS VIA DIFFERENT SIGNALING PATHWAYS IN L6 SKELETAL-MUSCLE CELLS (VOL 421, PG 120, 1998)

It was recently demonstrated that dexamethasone treatment of L6 skelet al muscle cells resulted in an elevation of GLUT1 protein, However, th e level of GLUT4 protein under these conditions was not examined, In a ddition, the signalling mechanism(s) leading to dexamethasone-induced expression of GLUT1 protein was not investigated, In the present study we investigated the effect of dexamethasone on the expression of GLUT 1 and GLUT4 proteins in differentiated L6 muscle cells and the signall ing mechanism(s) via which dexamethasone may act, Dexamethasone (300 n M) treatment for 24 h elevated GLUT1 and GLUT4 proteins by 68% and 94% , respectively, above control levels, These increases were due to de n ovo synthesis as shown by metabolic labelling with [S-35]methionine. i ncubation of cells with 100 nM wortmannin or 30 ng/ml rapamycin preven ted the dexamethasone-stimulated elevation of GLUT1 protein, In contra st, neither of these inhibitors affected the elevation of GLUT4 protei n by dexamethasone, Furthermore, dexamethasone down-regulated insulin receptor substrate-1 protein content by 32% and insulin-induced tyrosi ne phosphorylation of insulin receptor substrate-1 by 28%. The p70 rib osomal S6 kinase was not activated by dexamethasone and instead, dexam ethasone attenuated the stimulation of this enzyme activity by insulin , These results suggest that dexamethasone induces the expression of G LUT1 and GLUT4 protein by independent signalling mechanisms with a con comitant depression of intracellular signalling by insulin. (C) 1998 F ederation of European Biochemical Societies.