TYRAMINE AND VANADATE SYNERGISTICALLY STIMULATE GLUCOSE-TRANSPORT IN RAT ADIPOCYTES BY AMINE OXIDASE-DEPENDENT GENERATION OF HYDROGEN-PEROXIDE

Nonadrenergic imidazoline I-2-binding sites colocalize with monoamine oxidase (MAO) in various tissues. As white adipocytes from various spe cies have been reported to be very rich in I-2-sites, the authors cons ider whether these cells show a substantial MAO activity and explore i ts functional role. Oxidation of [C-14]tyramine by rat adipocyte membr anes was dependent on both MAO and semicarbazide-sensitive amine oxida se (SSAO). Tyramine oxidation was identical in membranes and in intact adipocytes (V-max 11-12 nmol/min/mg protein). A similar effect of MAO and SSAO inhibitors was obtained in both the intact cells and the mem branes: half of the activity was sensitive to semicarbazide and the ot her half more easily inhibited by MAO-A than by MAO-B inhibitors. As t he reaction catalyzed by amine oxidases generates H2O2, which mimicks certain insulin effects in adipocytes, we tested whether tyramine oxid ation influences glucose transport in adipocytes. One mM tyramine weak ly stimulated glucose transport. A clear potentiation of tyramine effe ct occurred in the presence of 0.1 mM vanadate, ineffective by itself, reaching half-maximal insulin stimulation. This stimulation was sensi tive to MAO and SSAO inhibitors and to catalase. The 5-fold activation of glucose transport was accompanied by translocation of GLUT4 transp orters to the plasma membrane. This shows that tyramine is readily oxi dized 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.