Hydroxylamine, a nitric oxide donor, inhibits insulin release and activates K+ATP channels.
The present study was undertaken to assess the effects of hydroxylamine, a nitric oxide (NO) donor, on ionic and secretory events in rat pancreatic islets. Hydroxylamine provoked a concentration-dependent inhibition of the glucose-induced insulin release. This inhibitory action was counteracted by glibenclamide. Moreover, hydroxylamine increased the rate of 86Rb outflow from perifused islets. This effect persisted in the absence of external Ca2+ but was impaired by glibenclamide. Hydroxylamine decreased 45Ca outflow, [Ca2+]i and insulin output from islets exposed to 16.7 mM glucose and extracellular Ca2+. By contrast, hydroxylamine did not affect the increase in 45Ca outflow and [Ca2+]i evoked by K+ depolarization. These experimental results suggest that the negative insulinotropic action of the NO donor results, at least in part, from the activation of ATP-sensitive K+ channels leading to a decrease in Ca2+ influx and [Ca2+]i. Additional mechanisms, however, could also be involved in the NO donor modulation of the secretory process.
Laboratory of Pharmacology, Université Libre de Bruxelles, School of Medicine (Bât. GE-CP 617), Belgium.
M H
MH
Antoine
R
R
Ouedraogo
J
J
Sergooris
M
M
Hermann
A
A
Herchuelz
P
P
Lebrun
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D002132:Calcium Radioisotopes; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012413:Rubidium / Q000493:pharmacokinetics; D012414:Rubidium Radioisotopes; D012680:Sensitivity and Specificity; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D006898:Hydroxylamines; D007328:Insulin; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D019811:Hydroxylamine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D005947:Glucose; D012413:Rubidium; D002118:Calcium