---
pmid: '18541525'
title: Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances
  insulin sensitivity in skeletal muscle cells.
authors:
- 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
journal: J Biol Chem
year: '2008'
full_text_available: false
doi: 10.1074/jbc.M803771200
pubmed_publication_types:
- Journal Article
- Research Support, Non-U.S. Gov't
publication_type: PRIMARY_RESEARCH
---

# Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells.
**Authors:** 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
**Journal:** J Biol Chem (2008)
**DOI:** [10.1074/jbc.M803771200](https://doi.org/10.1074/jbc.M803771200)

## Abstract

1. J Biol Chem. 2008 Aug 1;283(31):21769-78. doi: 10.1074/jbc.M803771200. Epub
2008  Jun 9.

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

Viparelli F(1), 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.

Author information:
(1)Istituto di Biostrutture e Bioimmagini and Istituto di Endocrinologia e
Oncologia Sperimentale Gaetano Salvatore, Consiglio Nazionale delle Ricerche,
Naples, Italy.

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
mum), 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 approximately 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.

DOI: 10.1074/jbc.M803771200
PMID: 18541525 [Indexed for MEDLINE]