DEXAMETHASONE STIMULATES THE EXPRESSION OF GLUT1 AND GLUT4 PROTEINS VIA DIFFERENT SIGNALING PATHWAYS IN L6 SKELETAL-MUSCLE CELLS

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 nas not examined, In a ddition, the signalling mechanism(s) leading to dexamethasone-induced expression of GLUT1 protein nas 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 prote in by dexamethasone. Furthermore, dexamethasone down-regulated insulin receptor substrate-1 protein content by 42%, and insulin-induced tyro sine phosphor lation of insulin receptor substrate-1 by 28%. The p70 r ibosomal S6 kinase was not activated by dexamethasone and instead, dex amethasone attenuated the stimulation of this enzyme activity by insul in. These results suggest that dexamethasone induces the expression of GLUT1 and GLUT4 protein by independent signalling mechanisms with a c oncomitant depression of intracellular signalling by insulin, (C) 1998 Federation of European Biochemical Societies.