Nitric oxide and hydroperoxide affect islet hormone release and Ca2+ efflux
Nitric oxide and hydroperoxide affect islet hormone release and Ca2+ efflux
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DOI：
10.1385/endo:11:1:99
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发表时间：
1999-08-01
期刊：
影响因子：
3.7
通讯作者：
Lundquist, I
中科院分区：
文献类型：
--
作者：
Åkesson, B;Lundquist, I
我们研究了细胞内自由基供体羟胺（产生一氧化氮[NO]）和叔丁基过氧化氢（产生氢过氧化物[“H2 O2”]）对葡萄糖和环磷酸腺苷（cAMP）诱导的胰岛激素释放转导信号的影响。两种供体均剂量依赖性地抑制葡萄糖刺激的胰岛素释放，并诱导中度（羟胺）或深度（叔丁基过氧化氢）抑制灌流胰岛的Ca-45（2+）流出。相比之下，两种供体均刺激胰高血糖素释放。钾离子去极化后激素释放也有类似的作用。胰岛素和胰高血糖素释放刺激的cAMP系统的激活，通过异丁基甲基黄嘌呤（IBMX）在基础葡萄糖适度增强低浓度的两个捐助者。在K+去极化胰岛中仍然观察到这些效应，尽管不太明显。在体外和体内，NO合酶抑制剂N-G-硝基-L-精氨酸甲酯抑制IBMX诱导的胰高血糖素释放，但不影响胰岛素释放。结果表明，NO和氢过氧化物抑制葡萄糖刺激的胰岛素释放的扰动Ca 2+流量，并可能通过S-亚硝基化（NO）或氧化（氢过氧化物）的巯基分泌过程中的关键作用。这些效应在很大程度上与去极化事件无关。相比之下，NO和氢过氧化物可以增强cAMP刺激的激素释放，推测在刺激分泌耦合的远端位点。
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 Ca-45(2+)-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 N-G-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.