terminal BET bromodomain inhibitors disrupt a BRD4-p65 interaction and reduce inducible nitric oxide synthase transcription in pancreatic β-cells.

Chronic inflammation of pancreatic islets is a key driver of β-cell damage that can lead to autoreactivity and the eventual onset of autoimmune diabetes (T1D). In the islet, elevated levels of proinflammatory cytokines induce the transcription of the inducible nitric oxide synthase (iNOS) gene, , ultimately resulting in increased nitric oxide (NO). Excessive or prolonged exposure to NO causes β-cell dysfunction and failure associated with defects in mitochondrial respiration.