"Cytokine-induced human islet cell death in vitro correlateswith a persistently high phosphorylation of STAT-1, but not with Access to the published version may require subscription. ABSTRACTStudies of insulin producing -cells have reported conflicting responses to NF-κB activation, encompassing both pro-and anti-apoptotic effects, possibly reflecting the use of -cells from different species. Therefore, the aim of this study was to compare the temporal activation of NF-κB in rat and human insulin producing cells and relate this to the dynamics of cell death, STAT-1 activation and the production of nitric oxide (NO). Rat RIN5AH and human islet cells were exposed to the cytokines IL-1 and IFN- and the NOS inhibitor aminoguanidine. Cell death, NO production,  phosphorylation, p65 methylation, STAT-1 phosphorylation and cIAP-2 levels were analyzed at different time-points. Cytokine-induced RIN5AH cell death occurred on day 1, and this was paralleled by NF-B activation, STAT-1 phosphorylation and production of NO. On the other hand, the human islet cells instead died by an NO-independent mechanism on day 3and 5. This later occurring cell death was associated with a gradual decrease in  phosphorylation and p65 methylation, and a lowered expression of the NF-B target genes  and cIAP-2. STAT-1 phosphorylation was persistently high during the entire cytokine exposure period in human islet cells. The results favor a pro-survival role of NF-B and a pro-apoptotic role of STAT-1 in human islet cells. Thus, rodent insulin producing cells may not be suitable as models for human -cells in the context of cytokine-induced damage.