Gi-mediated translocation of GLUT4 is independent of p85/p110alpha and p110gamma phosphoinositide 3-kinases but might involve the activation of Akt kinase.
Activation of phosphoinositide 3-kinase (PI-3K) is essential for insulin-stimulated translocation of GLUT4 and glucose transport in insulin target tissues. A novel p110gamma PI-3K was reported to be activated by G(i)-coupled receptors via Gbetagamma subunits. We asked whether the stimulation of G(i)-coupled receptors would trigger GLUT4 translocation and glucose uptake by the activation of Gbetagamma-dependent p110gamma PI-3K. We find that this translocation and glucose uptake can be induced by the ligand stimulation of G(i)-coupled alpha(2A) adrenergic receptor and fMet-Leu-Phe receptor in cells stably expressing these receptors. The noradrenaline ('noradrenaline')- and fMet-Leu-Phe-stimulated GLUT4 translocations were abolished by pretreatment with pertussis toxin. Pretreatment with wortmannin or genistein also inhibited the G(i)-mediated GLUT4 translocation. On ligand stimulation of these two kinds of G(i)-coupled receptor, although there was a slight increase in PtdIns(3,4,5)P(3) production, activation of either the p85/p110alpha PI-3K or Gbetagamma-dependent p110gamma PI-3K was not observed even in Chinese hamster ovary cells stably overexpressing exogenous p101/p110gamma. The G(i)-mediated GLUT4 translocation was accompanied by activation of the serine-threonine kinase Akt; the inhibitory effects of pertussis toxin, wortmannin and genistein on G(i)-mediated GLUT4 translocation paralleled their inhibitory effects on Akt activation. In contrast, the activation of some other G(i)-coupled receptors, such as prostaglandin EP3alpha receptor and platelet-activating factor receptor, did not cause either pertussis-toxin-sensitive translocation of GLUT4myc or activation of Akt kinase. These results indicate that the ligand stimulation of some G(i)-coupled receptors triggers GLUT4 translocation that occurs independently of p85/p110alpha-type and p110gamma-type PI-3Ks but might involve the activation of Akt kinase.
Wang
L
L
Division of Molecular Genetics, Institute for Enzyme Research, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Hayashi
H
H
Kishi
K
K
Huang
L
L
Hagi
A
A
Tamaoka
K
K
Hawkins
P T
PT
Ebina
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D016259:Genes, myc; D019833:Genistein / Q000494:pharmacology; D005947:Glucose / Q000493:pharmacokinetics; D051275:Glucose Transporter Type 4; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
D000316:Adrenergic alpha-Agonists; D000730:Androstadienes; D004791:Enzyme Inhibitors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019833:Genistein; D005947:Glucose; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009638:Norepinephrine; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010980:Platelet Membrane Glycoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018341:Receptors, Adrenergic, alpha-2; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D018078:Receptors, Prostaglandin E; D010566:Virulence Factors, Bordetella; D000077191:Wortmannin; C060974:phosphatidylinositol 3,4,5-triphosphate; C039351:platelet activating factor receptor