FIG. 5.

Proposed model for the dual regulation of DDR by nitric oxide during cytokine exposure. During short exposure to cytokines (0–24 h), the high rates of nitric oxide production suppress DDR signaling despite causing DNA damage. Under these conditions, the DDR cannot initiate apoptosis and β cells are able to recover and survive. When cytokine exposure lengthens (>36 h) and cellular damage increases, the rates of nitric oxide production decrease by sixfold and allow for DDR activation and DDR-dependent apoptosis. iNOS, isoform of nitric oxide synthase.