The effect of DFMO on the gene expression in pro-inflammatory cytokine-treated human islets
Inhibition of polyamine biosynthesis using a-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), reduces ß-cell stress and type 1 diabetes (T1D) incidence in preclinical models. However, underlying cellular and molecular mechanisms and the tolerability and effectiveness of polyamine depletion by DFMO in humans with T1D remain unknown. Transcriptomics and proteomics of cytokine-stressed human islets treated with DFMO reveal alterations in mRNA translation, nascent protein transport, and secretion. Collectively, our data suggest that inhibition of polyamine biosynthesis may preserve ß-cell function in T1D via islet cell-autonomous responses to stress. Overall design: Comparative gene expression profiling analysis of RNA-seq data for human islets treated with DFMO in presence or absence of proinflammatory cytokines