Nitric oxide induces synchronous Ca2+ transients in pancreatic beta cells lacking contact.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
The results support the idea that nitrergic nerves generate beta-cell transients of Ca2+ synchronizing the activity of the numerous islets in the pancreas.
Grapengiesser
E
E
Department of Medical Cell Biology, Biomedicum, Uppsala University, SE-75 123 Uppsala, Sweden.
Gylfe
E
E
Dansk
H
H
Hellman
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D019811:Hydroxylamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology*; D051379:Mice; D008820:Mice, Obese; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D010507:Periodicity; D015398:Signal Transduction
D007328:Insulin; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019811:Hydroxylamine; D009569:Nitric Oxide; D005934:Glucagon; D002118:Calcium