Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells. (Articolo in rivista)

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  • Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1074/jbc.M803771200 (literal)
Alternative label
  • Viparelli F; Cassese A; Doti N; Paturzo F; Marasco D; Dathan NA; Monti SM; Basile G; Ungaro P; Sabatella M; Miele C; Teperino R; Consiglio E; Pedone C; Beguinot F; Formisano P; Ruvo M. (2008)
    Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells.
    in Journal of biological chemistry (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Viparelli F; Cassese A; Doti N; Paturzo F; Marasco D; Dathan NA; Monti SM; Basile G; Ungaro P; Sabatella M; Miele C; Teperino R; Consiglio E; Pedone C; Beguinot F; Formisano P; Ruvo M. (literal)
Pagina inizio
  • 21769 (literal)
Pagina fine
  • 21778 (literal)
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  • 283 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 31 (literal)
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  • Pubblicazione su rivista internazionale (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto di Biostrutture e Bioimmagini and ¶Istituto di Endocrinologia e Oncologia Sperimentale Gaetano Salvatore, Consiglio Nazionale delle Ricerche, Naples 80134, the §Dipartimento di Scienze Biologiche and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita` di Napoli Federico II, Naples 80131, Dipartimento di Biochimica e Biofisica, Seconda Universita` di Napoli, 80134 Naples, and Tecnogen SpA, Localita` La Fagianeria, 81015 Piana di Monte Verna, Caserta, Italy (literal)
Titolo
  • Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells. (literal)
Abstract
  • Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) is overexpressed in several tissues of individuals affected by type 2 diabetes. In intact cells and in transgenic animal models, PED/PEA-15 overexpression impairs insulin regulation of glucose transport, and this is mediated by its interaction with the C-terminal D4 domain of phospholipase D1 (PLD1) and the consequent increase of protein kinase C-alpha activity. Here we show that interfering with the interaction of PED/PEA-15 with PLD1 in L6 skeletal muscle cells overexpressing PED/PEA-15 (L6(PED/PEA-15)) restores insulin sensitivity. Surface plasmon resonance and ELISA-like assays show that PED/PEA-15 binds in vitro the D4 domain with high affinity (K-D = 0.37 +/- 0.13 mu M), and a PED/PEA-15 peptide, spanning residues 1-24, PED-(1-24), is able to compete with the PED/PEA-15-D4 recognition. When loaded into L6(PED/PEA-15) cells and in myocytes derived from PED/PEA-15-overexpressing transgenic mice, PED-(1-24) abrogates the PED/PEA-15-PLD1 interaction and reduces protein kinase C-alpha activity to levels similar to controls. Importantly, the peptide restores insulin-stimulated glucose uptake by similar to 70%. Similar results are obtained by expression of D4 in L6(PED/PEA-15). All these findings suggest that disruption of the PED/PEA-15-PLD1 molecular interaction enhances insulin sensitivity in skeletal muscle cells and indicate that PED/PEA-15 as an important target for type 2 diabetes. (literal)
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