AIMS: To evaluate the role of nitric oxide (NO) in the coordination of the Ca2+ signals generating pulsatile insulin release in pancreatic beta cells isolated from ob/ob mice. METHODOLOGY: Using ratiometric fura-2 technique for recording glucose-induced cytoplasmic Ca2+ transients, it was possible to demonstrate a synchronization of beta 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 beta cells were exposed to 100 microM of the NO donors sodium nitroprusside and hydroxylamine. Bolus additions of 0.1-10 microM gaseous NO resulted in prompt appearance of cytoplasmic Ca2+ 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 beta-cell transients of Ca2+ synchronizing the activity of the numerous islets in the pancreas.
AIMS: To evaluate the role of nitric oxide (NO) in the coordination of the Ca2+ signals generating pulsatile insulin release in pancreatic beta cells isolated from ob/ob mice. METHODOLOGY: Using ratiometric fura-2 technique for recording glucose-induced cytoplasmic Ca2+ transients, it was possible to demonstrate a synchronization of beta 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 beta cells were exposed to 100 microM of the NO donors sodium nitroprusside and hydroxylamine. Bolus additions of 0.1-10 microM gaseous NO resulted in prompt appearance of cytoplasmic Ca2+ 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 beta-cell transients of Ca2+ synchronizing the activity of the numerous islets in the pancreas.
Authors: Nikki L Farnsworth; Rachelle L Walter; Alireza Hemmati; Matthew J Westacott; Richard K P Benninger Journal: J Biol Chem Date: 2015-12-14 Impact factor: 5.157