Gq-coupled receptors transmit the signal for GLUT4 translocation via an insulin-independent pathway.
Guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) induces the translocation of glucose transporter type 4 (GLUT4) from an intracellular pool to the cell surface and increases glucose uptake in adipocytes. The GTP-binding protein(s) responsible for the translocation has remained to be identified. Using a sensitive and quantitative method to assess the translocation of c-MYC epitope-tagged GLUT4, we obtained evidence that the activation of receptor-coupled Gq (neither Gi nor Gs) triggered GLUT4 translocation in cells, independently of insulin signaling pathway(s). Platelet-activating factor (PAF) induced GLUT4 translocation in the cells expressing the Gi- and Gq-coupled PAF receptor, but the translocation was induced even after pretreatment with wortmannin, an islet-activating protein and phorbol 12, 13-dibutyrate. Norepinephrine triggered GLUT4 translocation in cells expressing the Gq-coupled alpha1-adrenergic receptor, but prostaglandin E2 did not cause GLUT4 translocation in cells expressing the Gs-coupled EP4 receptor or the Gi-coupled EP3alpha receptor. The norepinephrine-stimulated GLUT4 translocation and glucose uptake via Gq may possibly contribute to the fuel supply required for thermogenesis in brown adipocytes and for the enhanced contractility in cardiomyocytes, both of which have an abundant endogenous GLUT4.
Kishi
K
K
Department of Enzyme Genetics, Institute for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770, Japan.
Hayashi
H
H
Wang
L
L
Kamohara
S
S
Tamaoka
K
K
Shimizu
T
T
Ushikubi
F
F
Narumiya
S
S
Ebina
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009638:Norepinephrine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; C039351:platelet activating factor receptor; D019204:GTP-Binding Proteins; D005947:Glucose; D009638:Norepinephrine