title: A serum factor induces insulin-independent translocation of GLUT4 to the cell surface which is maintained in insulin resistance.
abstract: In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor.
authors.affiliation: INSERM, U895, Mediterranean Research Center for Molecular Medicine (C3M), Avenir Team 9, Nice, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Berenguer
authors.forename: Laurène
authors.initials: L
authors.lastname: Martinez
authors.forename: Sophie
authors.initials: S
authors.lastname: Giorgetti-Peraldi
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Marchand-Brustel
authors.forename: Roland
authors.initials: R
authors.lastname: Govers
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D011990:Receptors, Transferrin; C495692:SLC2A4 protein, human; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D005947:Glucose