title: Tyramine and vanadate synergistically stimulate glucose transport in rat adipocytes by amine oxidase-dependent generation of hydrogen peroxide.
abstract: Nonadrenergic imidazoline I2-binding sites colocalize with monoamine oxidase (MAO) in various tissues. As white adipocytes from various species have been reported to be very rich in I2-sites, the authors consider whether these cells show a substantial MAO activity and explore its functional role. Oxidation of [14C]tyramine by rat adipocyte membranes was dependent on both MAO and semicarbazide-sensitive amine oxidase (SSAO). Tyramine oxidation was identical in membranes and in intact adipocytes (Vmax: 11-12 nmol/min/mg protein). A similar effect of MAO and SSAO inhibitors was obtained in both the intact cells and the membranes: half of the activity was sensitive to semicarbazide and the other half more easily inhibited by MAO-A than by MAO-B inhibitors. As the reaction catalyzed by amine oxidases generates H2O2, which mimicks certain insulin effects in adipocytes, we tested whether tyramine oxidation influences glucose transport in adipocytes. One mM tyramine weakly stimulated glucose transport. A clear potentiation of tyramine effect occurred in the presence of 0.1 mM vanadate, ineffective by itself, reaching half-maximal insulin stimulation. This stimulation was sensitive to MAO and SSAO inhibitors and to catalase. The 5-fold activation of glucose transport was accompanied by translocation of GLUT4 transporters to the plasma membrane. This shows that tyramine is readily oxidized by adipocytes and potentiates the effects of vanadium on glucose transport through release of hydrogen peroxide. The role of the amine oxidases, which are highly expressed in adipocytes, allows them to be considered as more than mere scavengers of circulating amines.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM U 317), Institut Louis Bugnard, Université Paul SABATIER, C.H.U. Rangueil, 31403 Toulouse Cedex 4, France.
authors.forename: L
authors.initials: L
authors.lastname: Marti
authors.forename: N
authors.initials: N
authors.lastname: Morin
authors.forename: G
authors.initials: G
authors.lastname: Enrique-Tarancon
authors.forename: D
authors.initials: D
authors.lastname: Prevot
authors.forename: M
authors.initials: M
authors.lastname: Lafontan
authors.forename: X
authors.initials: X
authors.lastname: Testar
authors.forename: A
authors.initials: A
authors.lastname: Zorzano
authors.forename: C
authors.initials: C
authors.lastname: Carpéné
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D001692:Biological Transport; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014439:Tyramine / Q000378:metabolism / Q000494:pharmacology*; D014638:Vanadates / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D014638:Vanadates; D006861:Hydrogen Peroxide; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D005947:Glucose; D014439:Tyramine