Interleukin 1 beta increases the cytosolic free sodium concentration in isolated rat islets of Langerhans.

Interleukin 1 (IL-1) exerts both stimulatory and inhibitory (cytotoxic) effects on insulin-producing beta cells in isolated pancreatic islets. Since alteration in ion fluxes is crucial for endocrine cell activation and is a denominator of cell death, and since IL-1 was recently shown to increase the total sodium content in a murine pre-B-lymphocyte cell line, we investigated the effect of recombinant human IL-1 beta (rhIL-1 beta) on the cytosolic free sodium concentration (fNa+i) in rat islets. Furthermore, long-term rhIL-1 beta effects on islet cell function were studied during exposure of islets to amiloride, a blocker of the plasma membrane Na+/H+ exchange. One hour of islet exposure to 60 U/ml of rhIL-1 beta caused a threefold increase in fNa+i in islet cells, and this effect was abolished by depletion of extracellular sodium. Blockade of Na+/H+ exchange with amiloride abolished the inhibitory effect of rhIL-1 beta on insulin release. In conclusion, rhIL-1 beta was found to increase sodium influx in pancreatic islet cells. This might underlie the widespread effects of rhIL-1 beta on beta-cell function and morphology, possibly related to IL-1-mediated toxic free radical formation.