Gi-mediated translocation of GLUT4 is independent of p85/p110alpha and p110gamma phosphoinositide 3-kinases but might involve the activation of Akt kinase

Biochem J. 2000 Feb 1;345 Pt 3(Pt 3):543-55.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Amino Acid Sequence
  • Androstadienes / pharmacology
  • Animals
  • Biological Transport / drug effects
  • CHO Cells / metabolism
  • Cricetinae
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Genes, myc
  • Genistein / pharmacology
  • Glucose / pharmacokinetics
  • Glucose Transporter Type 4
  • Molecular Sequence Data
  • Monosaccharide Transport Proteins / drug effects
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Norepinephrine / pharmacology
  • Pertussis Toxin
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Platelet Membrane Glycoproteins / drug effects
  • Platelet Membrane Glycoproteins / metabolism
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Cell Surface*
  • Receptors, Formyl Peptide
  • Receptors, G-Protein-Coupled*
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Peptide / drug effects
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Receptors, Prostaglandin E / drug effects
  • Receptors, Prostaglandin E / metabolism
  • Virulence Factors, Bordetella / pharmacology
  • Wortmannin

Substances

  • Adrenergic alpha-Agonists
  • Androstadienes
  • Enzyme Inhibitors
  • Glucose Transporter Type 4
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Phosphatidylinositol Phosphates
  • Platelet Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Receptors, Adrenergic, alpha-2
  • Receptors, Cell Surface
  • Receptors, Formyl Peptide
  • Receptors, G-Protein-Coupled
  • Receptors, Immunologic
  • Receptors, Peptide
  • Receptors, Prostaglandin E
  • Virulence Factors, Bordetella
  • phosphatidylinositol 3,4,5-triphosphate
  • platelet activating factor receptor
  • Phorbol 12,13-Dibutyrate
  • N-Formylmethionine Leucyl-Phenylalanine
  • Genistein
  • Pertussis Toxin
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Glucose
  • Norepinephrine
  • Wortmannin