Activation of phosphoinositide 3-kinase (PI-3K) is essential for insulin-stimulated translocation of GLUT4 and glucose transport in insulin target tissues. A novel p110γ PI-3K was reported to be activated by Gi-coupled receptors via Gβγ subunits. We asked whether the stimulation of Gi-coupled receptors would trigger GLUT4 translocation and glucose uptake by the activation of Gβγ-dependent p110γ PI-3K. We find that this translocation and glucose uptake can be induced by the ligand stimulation of Gi-coupled α2A 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 Gi-mediated GLUT4 translocation. On ligand stimulation of these two kinds of Gi-coupled receptor, although there was a slight increase in PtdIns(3,4,5)P3 production, activation of either the p85/p110α PI-3K or Gβγ-dependent p110γ PI-3K was not observed even in Chinese hamster ovary cells stably overexpressing exogenous p101/p110γ. The Gi-mediated GLUT4 translocation was accompanied by activation of the serine-threonine kinase Akt; the inhibitory effects of pertussis toxin, wortmannin and genistein on Gi-mediated GLUT4 translocation paralleled their inhibitory effects on Akt activation. In contrast, the activation of some other Gi-coupled receptors, such as prostaglandin EP3α 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 Gi-coupled receptors triggers GLUT4 translocation that occurs independently of p85/p110α-type and p110γ-type PI-3Ks but might involve the activation of Akt kinase.
Gi-mediated translocation of GLUT4 is independent of p85/p110α and p110γ phosphoinositide 3-kinases but might involve the activation of Akt kinase
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Lihong WANG, Hideki HAYASHI, Kazuhiro KISHI, Luping HUANG, Akifumi HAGI, Keisuke TAMAOKA, Phillip T. HAWKINS, Yousuke EBINA; Gi-mediated translocation of GLUT4 is independent of p85/p110α and p110γ phosphoinositide 3-kinases but might involve the activation of Akt kinase. Biochem J 1 February 2000; 345 (3): 543–555. doi: https://doi.org/10.1042/bj3450543
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