Na+,K+‐ATPase trafficking in skeletal muscle: insulin stimulates translocation of both α1‐ and α2‐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 α2‐ but not α1‐subunits was detected. However, using cell surface biotinylation techniques, an insulin‐induced membrane translocation of both α1 and α2‐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 α1‐ and α2‐subunit translocation to the skeletal muscle plasma membrane via a PI 3‐kinase‐dependent mechanism.