A novel inhibitor of inducible NOS dimerization protects against cytokine-induced rat beta cell dysfunction.

ABSTRACT:

Background and purpose

Beta cell apoptosis is a major feature of type 1 diabetes, and pro-inflammatory cytokines are key drivers of the deterioration of beta cell mass through induction of apoptosis. Mitochondrial stress plays a critical role in mediating apoptosis by releasing cytochrome C into the cytoplasm, directly activating caspase-9 and its downstream signalling cascade. We aimed to identify new compounds that protect beta cells from cytokine-induced activation of the intrinsic (mitochondrial) pathway of apoptosis.

Experimental approach

Diabetogenic media, composed of IL-1β, IFN-γ and high glucose, were used to induce mitochondrial stress in rat insulin-producing INS1E cells, and a high-content image-based screen of small molecule modulators of Casp9 pathway was perfo

SUBMITTER: Zhong L 

PROVIDER: S-EPMC6086989 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature