Peroxisome proliferator-activated receptor-? activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1. (Articolo in rivista)

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  • Peroxisome proliferator-activated receptor-? activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1. (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Alternative label
  • Ungaro P, Mirra P, Oriente F, Nigro C, Ciccarelli M, Vastolo V, Longo M, Perruolo G, Spinelli R, Formisano P, Miele C, Beguinot F. (2012)
    Peroxisome proliferator-activated receptor-? activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1.
    in The Journal of biological chemistry (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Ungaro P, Mirra P, Oriente F, Nigro C, Ciccarelli M, Vastolo V, Longo M, Perruolo G, Spinelli R, Formisano P, Miele C, Beguinot F. (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli \"Federico II\", Consiglio Nazionale delle Ricerche, 80131 Naples, Italy. pungaro@ieos.cnr.it (literal)
Titolo
  • Peroxisome proliferator-activated receptor-? activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1. (literal)
Abstract
  • The gene network responsible for inflammation-induced insulin resistance remains enigmatic. In this study, we show that, in L6 cells, rosiglitazone- as well as pioglitazone-dependent activation of peroxisome proliferator-activated receptor-? (PPAR?) represses transcription of the ped/pea-15 gene, whose increased activity impairs glucose tolerance in mice and humans. Rosiglitazone enhanced insulin-induced glucose uptake in L6 cells expressing the endogenous ped/pea-15 gene but not in cells expressing ped/pea-15 under the control of an exogenous promoter. The ability of PPAR? to affect ped/pea-15 expression was also lost in cells and in C57BL/6J transgenic mice expressing ped/pea-15 under the control of an exogenous promoter, suggesting that ped/pea-15 repression may contribute to rosiglitazone action on glucose disposal. Indeed, high fat diet mice showed insulin resistance and increased ped/pea-15 levels, although these effects were reduced by rosiglitazone treatment. Both supershift and ChIP assays revealed the presence of the AP-1 component c-JUN at the PED/PEA-15 promoter upon 12-O-tetradecanoylphorbol-13-acetate stimulation of the cells. In these experiments, rosiglitazone treatment reduced c-JUN presence at the PED/PEA-15 promoter. This effect was not associated with a decrease in c-JUN expression. In addition, c-jun silencing in L6 cells lowered ped/pea-15 expression and caused nonresponsiveness to rosiglitazone, although c-jun overexpression enhanced the binding to the ped/pea-15 promoter and blocked the rosiglitazone effect. These results indicate that PPAR? regulates ped/pea-15 transcription by inhibiting c-JUN binding at the ped/pea-15 promoter. Thus, ped/pea-15 is downstream of a major PPAR?-regulated inflammatory network. Repression of ped/pea-15 transcription might contribute to the PPAR? regulation of muscle sensitivity to insulin. (literal)
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