title: A role for protein kinase Bbeta/Akt2 in insulin-stimulated GLUT4 translocation in adipocytes.
abstract: Insulin stimulates glucose uptake into muscle and fat cells by promoting the translocation of glucose transporter 4 (GLUT4) to the cell surface. Phosphatidylinositide 3-kinase (PI3K) has been implicated in this process. However, the involvement of protein kinase B (PKB)/Akt, a downstream target of PI3K in regulation of GLUT4 translocation, has been controversial. Here we report that microinjection of a PKB substrate peptide or an antibody to PKB inhibited insulin-stimulated GLUT4 translocation to the plasma membrane by 66 or 56%, respectively. We further examined the activation of PKB isoforms following treatment of cells with insulin or platelet-derived growth factor (PDGF) and found that PKBbeta is preferentially expressed in both rat and 3T3-L1 adipocytes, whereas PKBalpha expression is down-regulated in 3T3-L1 adipocytes. A switch in growth factor response was also observed when 3T3-L1 fibroblasts were differentiated into adipocytes. While PDGF was more efficacious than insulin in stimulating PKB phosphorylation in fibroblasts, PDGF did not stimulate PKBbeta phosphorylation to any significant extent in adipocytes, as assessed by several methods. Moreover, insulin, but not PDGF, stimulated the translocation of PKBbeta to the plasma membrane and high-density microsome fractions of 3T3-L1 adipocytes. These results support a role for PKBbeta in insulin-stimulated glucose transport in adipocytes.
authors.affiliation: Centre for Molecular Biology, Department of Physiology, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: M M
authors.initials: MM
authors.lastname: Hill
authors.forename: S F
authors.initials: SF
authors.lastname: Clark
authors.forename: D F
authors.initials: DF
authors.lastname: Tucker
authors.forename: M J
authors.initials: MJ
authors.lastname: Birnbaum
authors.forename: D E
authors.initials: DE
authors.lastname: James
authors.forename: S L
authors.initials: SL
authors.lastname: Macaulay
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D015536:Down-Regulation; D004822:Epididymis / Q000166:cytology; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008845:Microinjections; D008861:Microsomes / Q000201:enzymology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009842:Oligopeptides / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009842:Oligopeptides; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D011494:Protein Kinases; C494920:Akt1 protein, rat; C494922:Akt2 protein, mouse; C494923:Akt2 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt