Role of cytokines in regulation of pancreatic B-cell function.

26 donor. This also distinguishes direct NO toxicity from 11,-1 toxicity. In the latter case, ionic fluxes were noted directly after the addition of the cytokine [ 151. In our experiment [CaZ+li started to increase progressively after 30 min until membrane rupture after approx. 3 h (not shown). This progressive calcium ion influx appeared to be closely associated with cell damage because nicotinamide, which has already been shown to prevent islet cell lysis [2], also inhibited cytosolic calcium accumulation (Figure 3b). W e assumed that the slow calcium influx was a consequence, rather than the cause, of cell membrane damage. This was supported by our discovery that chelation of CaL+ in the medium by EGTA did not prevent islet cell lysis (Figure 3c). On the contrary, addition of the calcium ionophore, A23 187, suppressed NO toxicity. This indicated that either A23 187 or the resulting elevated intracellular calcium levels interfere with a critical step of the NO toxicity pathway in islet cells.