title: Insulin-induced Effects on the Subcellular Localization of AKT1, AKT2 and AS160 in Rat Skeletal Muscle.
abstract: AKT1 and AKT2, the AKT isoforms that are highly expressed in skeletal muscle, have distinct and overlapping functions, with AKT2 more important for insulin-stimulated glucose metabolism. In adipocytes, AKT2 versus AKT1 has greater susceptibility for insulin-mediated redistribution from cytosolic to membrane localization, and insulin also causes subcellular redistribution of AKT Substrate of 160 kDa (AS160), an AKT2 substrate and crucial mediator of insulin-stimulated glucose transport. Although skeletal muscle is the major tissue for insulin-mediated glucose disposal, little is known about AKT1, AKT2 or AS160 subcellular localization in skeletal muscle. The major aim of this study was to determine insulin's effects on the subcellular localization and phosphorylation of AKT1, AKT2 and AS160 in skeletal muscle. Rat skeletal muscles were incubated ex vivo ± insulin, and differential centrifugation was used to isolate cytosolic and membrane fractions. The results revealed that: 1) insulin increased muscle membrane localization of AKT2, but not AKT1; 2) insulin increased AKT2 phosphorylation in the cytosol and membrane fractions; 3) insulin increased AS160 localization to the cytosol and membranes; and 4) insulin increased AS160 phosphorylation in the cytosol, but not membranes. These results demonstrate distinctive insulin effects on the subcellular redistribution of AKT2 and its substrate AS160 in skeletal muscle.
authors.affiliation: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.|Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.|Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Cartee
mesh_terms: D000730:Androstadienes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D020690:GTPase-Activating Proteins; D007328:Insulin; C533101:TBC1D4 protein, rat; C494920:Akt1 protein, rat; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin