STIMULATION OF MAP KINASE AND S6 KINASE BY VANADIUM AND SELENIUM IN RAT ADIPOCYTES

To explore the mechanism underlying the insulin-mimetic actions of van adium and selenium we examined their effects on the mitogen activated protein/myelin basic protein kinases (MAPK) and ribosomal S6 protein k inases, which are among the best characterized of the kinases that com prise the phosphorylation cascade in insulin signal transduction. We o bserved a transient activation of MAPK and S6 kinases by insulin in ra t adipocytes, while both sodium selenate and vanadyl sulphate produced prolonged activation of the kinases. Vanadyl sulphate stimulated the activity of MAPK and S6 kinase by as much as 6 fold and 15 fold, respe ctively. Pretreatment of the cells with genistein did not affect the a ctivation of MAPK by insulin, but partially blocked the effects of sod ium selenate and vanadyl sulphate. Genistein did not change the activa tion of S6 kinase by insulin, but blocked the activation in vanadyl su lphate-and sodium selenate-treated-cells, suggesting that a genistein sensitive tyrosine kinase may be involved in the activation by these t wo compounds. Rapamycin, a specific inhibitor of the p70s6k isoform of S6 kinase, partially reduced the activation of S6 kinase activity by sodium selenate, indicating a role for this kinase in the overall acti vity of the S6 kinase in sodium selenate-treated cells. A similar tren d was noted in vanadyl sulphate-treated cells. Thus, this study suppor ts the involvement of MAPK and S6 kinases in the insulin-mimetic actio ns of vanadium and selenium.