Na +,K +-ATPase trafficking in skeletal muscle: insulin stimulates translocation of both α 1- and α 2-subunit isoforms

Abstract

We determined insulin-stimulated Na +,K +-ATPase isoform-specific translocation to the skeletal muscle plasma membrane. When rat muscle plasma membrane fractions were isolated by discontinuous sucrose gradients, insulin-stimulated translocation of α 2- but not α 1-subunits was detected. However, using cell surface biotinylation techniques, an insulin-induced membrane translocation of both α 1 and α 2-subunits in rat epitrochlearis muscle and cultured human skeletal muscle cells was noted. Na +,K +-ATPase α-subunit translocation was abolished by the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin, as well as by the protein kinase C inhibitor GF109203X. Thus, insulin mediates Na +,K +-ATPase α 1- and α 2-subunit translocation to the skeletal muscle plasma membrane via a PI 3-kinase-dependent mechanism.