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pubmed:abstractText |
Protein kinase C?I (PKC?I) mediates insulin signaling and attenuates ?1-adrenoceptor-stimulated lipolysis. In this work, the effect of the PKC activator phorbol 12-myristate 13-acetate (PMA) on the antilipolytic action of insulin was determined by analyzing lipolysis induced by a ?3-adrenoceptor agonist CL 316243. PMA inhibited the insulin antilipolytic action. The pan-PKC inhibitors GF 109203X and chelerythrine inhibited the PMA effect, but the PKC?/? inhibitors Gö 6976 and CGP 53353 did not. Exposure of cells to PMA downregulated PKCs ?, ?I, and ? within 3 h and PKC? within 12 h. The effect of PMA on insulin action greatly diminished when PKC? was downregulated. Inhibitors of phosphatidylinositol 3-kinase (PI3-K), Akt, and phosphodiesterase 3B (PDE3B) diminished the PMA effect. PMA inhibited insulin-stimulated phosphorylation of Tyr in insulin receptor ? subunit and Ser/Thr in Akt. These data suggest that PMA inhibits the antilipolytic signal mediated by the insulin receptor, PI3-K, Akt, and PDE3B. The most probable target of PMA is PKC?.
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pubmed:affiliation |
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki-ken, 305-8575, Japan. jnakamur@md.tsukuba.ac.jp
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