Glucagon-like peptide 1 protects INS-1E mitochondria against palmitate-mediated beta-cell dysfunction: a proteomic study.
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.
Department of Pharmacy, University of Pisa, Pisa, Italy.
Federica
F
Ciregia
Laura
L
Giusti
Maurizio
M
Ronci
Marco
M
Bugliani
Isabella
I
Piga
Luisa
L
Pieroni
Claudia
C
Rossi
Piero
P
Marchetti
Andrea
A
Urbani
Antonio
A
Lucacchini
D000818:Animals; D002460:Cell Line; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010168:Palmitates / Q000633:toxicity*; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics; D051381:Rats
D007328:Insulin; D010168:Palmitates; D011506:Proteins; D020543:Proteome; D052216:Glucagon-Like Peptide 1