Nitric Oxide Induces Synchronous Ca 2+ Transients in Pancreatic β Cells Lacking Contact

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Abstract
Aims To evaluate the role of nitric oxide (NO) in the coordination of the Ca 2+ signals generating pulsatile insulin release in pancreatic β cells isolated from ob/ob mice. Methodology Using ratiometric fura-2 technique for recording glucose-induced cytoplasmic Ca 2+ transients, it was possible to demonstrate a synchronization of β cells lacking contact. Results The frequency of the transients increased 10-fold in the presence of 20 n M glucagon. Additional increase in frequency with maintenance of synchronization was observed when the β cells were exposed to 100 μM of the NO donors sodium nitroprusside and hydroxylamine. Bolus additions of 0.1–10 μM gaseous NO resulted in prompt appearance of cytoplasmic Ca 2+ transients. An activator of soluble guanylate cyclase (mesoporphyrin) increased the frequency of the transients, and inhibition of this enzyme with 1H-(1,2,4) oxadiazolo [4,3-a] quinoxalin-1-one had the opposite effect. Conclusion The results support the idea that nitrergic nerves generate β-cell transients of Ca 2+ synchronizing the activity of the numerous islets in the pancreas.