title: Dimethyl sulfoxide enhances GLUT4 translocation through a reduction in GLUT4 endocytosis in insulin-stimulated 3T3-L1 adipocytes.
abstract: Insulin increases muscle and fat cell glucose uptake by inducing the translocation of glucose transporter GLUT4 from intracellular compartments to the plasma membrane. Here, we have demonstrated that in 3T3-L1 adipocytes, DMSO at concentrations higher than 7.5% augmented cell surface GLUT4 levels in the absence and presence of insulin, but that at lower concentrations, DMSO only enhanced GLUT4 levels in insulin-stimulated cells. At a 5% concentration, DMSO also increased cell surface levels of the transferrin receptor and GLUT1. Glucose uptake experiments indicated that while DMSO enhanced cell surface glucose transporter levels, it also inhibited glucose transporter activity. Our studies further demonstrated that DMSO did not sensitize the adipocytes for insulin and that its effect on GLUT4 was readily reversible (t1/2∼12 min) and maintained in insulin-resistant adipocytes. An enhancement of insulin-induced GLUT4 translocation was not observed in 3T3-L1 preadipocytes and L6 myotubes, indicating cell specificity. DMSO did not enhance insulin signaling nor exocytosis of GLUT4 vesicles, but inhibited GLUT4 internalization. While other chemical chaperones (glycerol and 4-phenyl butyric acid) also acutely enhanced insulin-induced GLUT4 translocation, these effects were not mediated via changes in GLUT4 endocytosis. We conclude that DMSO is the first molecule to be described that instantaneously enhances insulin-induced increases in cell surface GLUT4 levels in adipocytes, at least in part through a reduction in GLUT4 endocytosis.
authors.affiliation: Inserm U895, Mediterranean Research Center for Molecular Medicine (C3M), Nice, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Berenguer
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Zhang
authors.forename: M Christine
authors.initials: MC
authors.lastname: Bruce
authors.forename: Laurène
authors.initials: L
authors.lastname: Martinez
authors.forename: Teresa
authors.initials: T
authors.lastname: Gonzalez
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Gurtovenko
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
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 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects*; D005089:Exocytosis; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D018832:Molecular Chaperones; D005947:Glucose; D004121:Dimethyl Sulfoxide