Glucagon-like peptide 1 protects INS-1E mitochondria against palmitate-mediated beta-cell dysfunction: A proteomic study

Federica Ciregia, Laura Giusti, Maurizio Ronci, Marco Bugliani, Isabella Piga, Luisa Pieroni, Claudia Rossi, Piero Marchetti, Andrea Urbani, Antonio Lucacchini

Research output: Contribution to journalArticle

Abstract

Prolonged exposure to palmitate impairs insulin secretion and leads to beta-cell death. Some evidence suggests that palmitate could induce these effects through defects in mitochondrial function. However, the mechanisms of lipotoxicity are not well understood. In particular, little is known about mitochondrial response to induced-palmitate stress and the mechanisms through which glucagon-like peptide-1 (GLP-1) exerts its potential protective effect in beta-cell mitochondrial dysfunction. The aim of this study was to analyze the protein expression profiles of enriched mitochondrial preparations of INS-1E beta-cells treated with palmitate in the presence and in the absence of GLP-1 using gel-based and gel-free proteomic approaches. INS1E beta-cells were incubated in the presence of 0.5 mM palmitate for 24 h, in the presence and in the absence of 10 nM GLP-1, and mitochondria were isolated. Co-incubation of palmitate-treated beta-cell lines with GLP-1 identified several GLP-1 responsive mitochondrial proteins from different functional classes indicating major changes in ATP production, oxidative stress, apoptosis, lipid and amino acid metabolism. Moreover, an interaction network analysis of proteins and metabolites found to be differentially expressed has been performed to understand the pathways involved in the palmitate and GLP-1 activity at the mitochondrial level. In summary, our results provided a snapshot of mitochondrial proteins and potential pathways affected by palmitate treatment and gave us information on the potential protective role of GLP-1.

Original languageEnglish
Pages (from-to)1696-1707
Number of pages12
JournalMolecular BioSystems
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2015

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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