Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal beta cells and human pancreatic islets

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Type 2 diabetes is characterized by progressive beta cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in beta cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E beta cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages beta cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in beta cell protein lysine acetylation and this modification could play a role in causing beta cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced beta cell lipotoxicity.
Lingua originaleEnglish
pagine (da-a)13445-13445
Numero di pagine1
RivistaScientific Reports
Volume7
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • N/A

Fingerprint

Entra nei temi di ricerca di 'Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal beta cells and human pancreatic islets'. Insieme formano una fingerprint unica.

Cita questo