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Journal of Diabetes Research
Volume 2014, Article ID 195739, 7 pages
Research Article

The Class I Histone Deacetylase Inhibitor MS-275 Prevents Pancreatic Beta Cell Death Induced by Palmitate

1European Genomic Institute for Diabetes (EGID) FR 3508, University of Lille, CNRS UMR 8199, and Faculty of Medicine West, 1 Place de Verdun, 59045 Lille, France
2Department of Endocrine Surgery, Lille University Hospital, INSERM UMR 859, University of Lille, EGID FR 3508, Biotherapies for Diabetes, Lille, France

Received 28 August 2014; Revised 26 November 2014; Accepted 7 December 2014; Published 31 December 2014

Academic Editor: Kazuya Yamagata

Copyright © 2014 Valérie Plaisance et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Elevation of the dietary saturated fatty acid palmitate contributes to the reduction of functional beta cell mass in the pathogenesis of type 2 diabetes. The diabetogenic effect of palmitate is achieved by increasing beta cell death through induction of the endoplasmic reticulum (ER) stress markers including activating transcription factor 3 (Atf3) and CAAT/enhancer-binding protein homologous protein-10 (Chop). In this study, we investigated whether treatment of beta cells with the MS-275, a HDAC1 and HDAC3 activity inhibitor which prevents beta cell death elicited by cytokines, is beneficial for combating beta cell dysfunction caused by palmitate. We show that culture of isolated human islets and MIN6 cells with MS-275 reduced apoptosis evoked by palmitate. The protective effect of MS-275 was associated with the attenuation of the expression of Atf3 and Chop. Silencing of HDAC3, but not of HDAC1, mimicked the effects of MS-275 on the expression of the two ER stress markers and apoptosis. These data point to HDAC3 as a potential drug target for preserving beta cells against lipotoxicity in diabetes.