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Nitric oxide and hydroperoxide affect islet hormone release and Ca2+ efflux

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Abstract

We have investigated the influence of the intracellular free radical donors hydroxylamine (giving nitric oxide [NO]) and tert-butylhydroperoxide (giving hydroperoxide [“H2O2”]) on glucose- and cyclic adenosine monophosphate (cAMP)-induced transduction signaling in islet hormone release. Both donors dose dependently inhibited glucose-stimulated insulin release and induced modest (hydroxylamine) or profound (tert-butylhydroperoxide) suppression of 45Ca2+-efflux from perifused islets. By contrast, both donors stimulated glucagon release. Similar effects on hormone release were displayed after K+-depolarization. Insulin and glucagon release stimulated by activation of the cAMP system through isobutylmethylxanthine (IBMX) at basal glucose was modestly potentiated by low concentrations of both donors. These effects were still observed, although less pronounced, in K+-depolarized islets. In vitro as well as in vivo, the NO-synthase inhibitor NG-nitro-L-arginine methyl ester inhibited IBMX-induced glucagon release, but did not affect insulin release. The results suggest that NO and hydroperoxide inhibit glucose-stimulated insulin release by perturbing Ca2+ fluxes and probably acting through S-nitrosylation (NO) or oxidation (hydroperoxide) of thiol groups critical to the secretory process. These effects are largely independent of depolarization events. By contrast, both NO and hydroperoxide can potentiate cAMP-stimulated hormone release presumably at a distal site in the stimulus-secretion coupling.

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Authors and Affiliations

  1. Department of Pharmacology, University of Lund, Sölvegatan 10, S-223 62, Lund, Sweden

    Björn Åkesson & Ingmar Lundquist

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  1. Björn Åkesson
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  2. Ingmar Lundquist
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Correspondence to Björn Åkesson.

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Åkesson, B., Lundquist, I. Nitric oxide and hydroperoxide affect islet hormone release and Ca2+ efflux. Endocr 11, 99–107 (1999). https://doi.org/10.1385/ENDO:11:1:99

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  • DOI: https://doi.org/10.1385/ENDO:11:1:99

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