title: Akt2 regulates Rac1 activity in the insulin-dependent signaling pathway leading to GLUT4 translocation to the plasma membrane in skeletal muscle cells.
abstract: The small GTPase Rac1 plays a pivotal role in insulin-stimulated glucose uptake in skeletal muscle, which is mediated by GLUT4 translocation to the plasma membrane. However, regulatory mechanisms for Rac1 and its role in the signaling pathway composed of phosphoinositide 3-kinase and the serine/threonine kinase Akt remain obscure. Here, we investigate the role of Akt in the regulation of Rac1 in myocytes. Insulin-induced, but not constitutively activated Rac1-induced, GLUT4 translocation was suppressed by Akt inhibitor IV. Insulin-induced Rac1 activation, on the other hand, was completely inhibited by this inhibitor. Constitutively activated phosphoinositide 3-kinase induced Rac1 activation and GLUT4 translocation. This GLUT4 translocation was almost completely suppressed by Rac1 knockdown. Furthermore, constitutively activated phosphoinositide 3-kinase-induced, but not constitutively activated Rac1-induced, GLUT4 translocation was suppressed by Akt2 knockdown. Finally, insulin-induced Rac1 activation was indeed inhibited by Akt2 knockdown. Together, these results reveal a novel regulatory mechanism involving Akt2 for insulin-dependent Rac1 activation.
authors.affiliation: Division of Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nozaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitaura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takenaka
authors.forename: Tohru
authors.initials: T
authors.lastname: Kataoka
authors.forename: Takaya
authors.initials: T
authors.lastname: Satoh
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein