Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion.
Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion.
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DOI：
10.1016/s0021-9258(18)54642-1
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发表时间：
1991-11
期刊：
影响因子：
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通讯作者：
J. A. Corbett;Jack R. Lancaster;M. Sweetland;M. L. McDaniel
中科院分区：
文献类型：
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作者：
J. A. Corbett;Jack R. Lancaster;M. Sweetland;M. L. McDaniel
白细胞介素（IL）-1抑制胰岛素分泌并最终导致胰腺β细胞破坏的分子机制仍不清楚。有证据表明，IL-1 β诱导的胰岛素分泌抑制依赖于L-精氨酸代谢为一氧化氮。NG-单甲基精氨酸是L-精氨酸依赖性酶一氧化氮合酶的竞争性抑制剂，可完全阻止IL-1诱导的对葡萄糖刺激的胰岛素分泌的抑制以及胰岛产生亚硝酸盐。进一步显示IL-1 β诱导胰岛中的一氧化氮形成，如g = 2.04的电子顺磁共振特征所证明的，其类似于先前报道的由一氧化氮破坏铁-硫中心形成的铁-亚硝酰基复合物。通过NG-单甲基精氨酸抑制一氧化氮合酶可完全阻止胰岛中EPR信号的形成。这些结果表明，IL-1诱导的胰岛素分泌抑制是通过一氧化氮的形成介导的，并表明一氧化氮的产生可能代表了负责β细胞破坏的细胞机制。
The molecular mechanism by which interleukin (IL)-1 inhibits insulin secretion and ultimately causes destruction of the pancreatic beta-cell remains unknown. Evidence is presented which suggests that IL-1 beta-induced inhibition of insulin secretion is dependent on the metabolism of L-arginine to nitric oxide. NG-Monomethylarginine, a competitive inhibitor of the L-arginine-dependent enzyme nitric oxide synthase, completely prevents IL-1-induced inhibition of glucose-stimulated insulin secretion as well as nitrite production by islets. It is further shown that IL-1 beta induces nitric oxide formation in islets as evidenced by an electron paramagnetic resonance feature at g = 2.04 which is similar to previously reported iron-nitrosyl complexes formed from the destruction of iron-sulfur centers by nitric oxide. Inhibition of the nitric oxide synthase by NG-monomethylarginine completely prevents the formation of this EPR signal in islets. These results show that IL-1-induced inhibition of insulin secretion is mediated through formation of nitric oxide and suggest that the generation of nitric oxide may represent the cellular mechanism responsible for beta-cell destruction.