Nitric oxide interferes with islet cell zinc homeostasis

Zinc is crucial for the biosynthesis, storage, and secretion of insulin in pancreatic islet cells. We have previously presented evidence that NO inter feres with cellular Zn2+ homeostasis and we therefore investigated the infl uence of chronic NO exposure on the labile islet cell Zn2+ content. A stron g fluorescence activity in a large islet cell subpopulation was found after staining with the Zn2+-specific fluorophore Zinquin. Culture for 24 h in t he presence of nontoxic concentrations of the slow-releasing NO donor DETA/ NO resulted in a significantly reduced Zn2+-dependent fluorescence. This ap pears to be islet specific as in endothelial cells DETA/NO exposure enhance d the Zn2+-dependent fluorescence activity in a concentration-dependent man ner. These results suggest that NO interferes with cellular Zn2+ homeostasi s, which in islet cells is crucial for proper hormone delivery and thus spe cial cell function. (C) 2000 Academic Press.