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.
Steno Memorial Hospital, Gentofte, Denmark.
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Helqvist
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PN
Bouchelouche
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Johannesen
J
J
Nerup
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000032:analysis / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012964:Sodium / Q000032:analysis* / Q000378:metabolism
D005609:Free Radicals; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D000584:Amiloride; D004247:DNA; D012964:Sodium; D010100:Oxygen