• HDAC inhibitors;
  • pancreatic β-cell;
  • inducible nitric oxide synthase;
  • NO release;
  • NF-κB


The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has recently been shown to inhibit deleterious effects of cytokines on β-cells, but it is unable to protect β-cells from death due to its own cytotoxicity. Herein, we investigated novel HDAC inhibitors for their cytoprotective effects against IL-1β-induced damage to isolated β-cells. We report that three novel compounds (THS-73–44, THS-72–5 and THS-78–5) significantly inhibited HDAC activity and increased the acetylation of histone H4 in isolated β-cells. Further, these compounds exerted no toxic effects on metabolic cell viability in these cells. However, among the three compounds tested, only THS-78–5 protected against IL-1β-mediated loss in β-cell viability. THS-78–5 was also able to attenuate IL-1β-induced inducible nitric oxide synthase expression and subsequent NO release. Our data also indicate that the cytoprotective properties of THS-78–5 against IL-1β-mediated effects may, in part, be due to inhibition of IL-1β-induced transactivation of nuclear factor κB (NF-κB) in these cells. Together, we provide evidence for a novel HDAC inhibitor with a significant potential to prevent IL-1β-mediated effects on isolated β-cells. Potential implications of these findings in the development of novel therapeutics to prevent deleterious effects of cytokines and the onset of autoimmune diabetes are discussed.