Nitric oxide and hydroperoxide affect islet hormone release and Ca(2+) efflux

Area of Science:

• Endocrinology
• Cell Signaling
• Free Radical Biology

Background:

• Intracellular free radicals play roles in cellular signaling.
• Nitric oxide (NO) and hydroperoxides (H2O2) are key signaling molecules.
• Their impact on pancreatic islet hormone release requires further elucidation.

Purpose of the Study:

• To investigate the effects of NO and H2O2 on glucose- and cyclic adenosine monophosphate (cAMP)-induced islet hormone release.
• To explore the mechanisms underlying these modulations, particularly concerning calcium (Ca2+) fluxes and stimulus-secretion coupling.

Main Methods:

• Utilized hydroxylamine and tert-butylhydroperoxide as NO and H2O2 donors, respectively.
• Assessed hormone release (insulin, glucagon) and 45Ca2+-efflux from perifused islets.
• Examined effects under basal, glucose-stimulated, K+-depolarized, and cAMP-stimulated conditions.
• Employed the NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester.

Main Results:

• Both NO and H2O2 dose-dependently inhibited glucose-stimulated insulin release and suppressed Ca2+ efflux.
• Glucagon release was stimulated by both donors, an effect also seen after K+-depolarization.
• Low concentrations of NO and H2O2 potentiated cAMP-stimulated insulin and glucagon release.
• NO-synthase inhibition affected glucagon but not insulin release in response to cAMP activation.

Conclusions:

• NO and hydroperoxide inhibit glucose-stimulated insulin release by disrupting Ca2+ fluxes, potentially via S-nitrosylation or oxidation of critical thiol groups.
• These inhibitory effects are largely independent of depolarization.
• Conversely, NO and hydroperoxide can potentiate cAMP-stimulated hormone release at a distal site in stimulus-secretion coupling.