Na+,K+-ATPase trafficking in skeletal muscle: insulin stimulates translocation of both alpha 1- and alpha 2-subunit isoforms.
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 alpha(2)- but not alpha(1)-subunits was detected. However, using cell surface biotinylation techniques, an insulin-induced membrane translocation of both alpha(1) and alpha(2)-subunits in rat epitrochlearis muscle and cultured human skeletal muscle cells was noted. Na(+),K(+)-ATPase alpha-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 alpha(1)- and alpha(2)-subunit translocation to the skeletal muscle plasma membrane via a PI 3-kinase-dependent mechanism.
Al-Khalili
Lubna
L
Section of Clinical Physiology, Department of Surgical Sciences, Integrative Physiology, Karolinska Institutet, von Eulers väg 4, 2 tr, SE-171 77 Stockholm, Sweden.
Yu
Mei
M
Chibalin
Alexander V
AV
D000818:Animals; D019921:Biotinylation; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D021122:Protein Subunits; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
D007328:Insulin; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D021122:Protein Subunits; D000254:Sodium-Potassium-Exchanging ATPase