Insulin secretion, DNA damage, and apoptosis in human and rat islets of Langerhans following exposure to nitric oxide, peroxynitrite, and cytokines.
Insulin secretion, DNA damage, and apoptosis in human and rat islets of Langerhans following exposure to nitric oxide, peroxynitrite, and cytokines.
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人类和大鼠胰岛暴露于一氧化氮、过氧亚硝酸盐和细胞因子后的胰岛素分泌、DNA 损伤和细胞凋亡。
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Irene C. Green
中科院分区：
文献类型：
--
作者：
V. Hadjivassiliou;M. Green;Michael H.L. Green;R. F. L. James;S. Swift;H. Clayton;Irene C. Green;Irene C. Green
自身免疫性糖尿病期间，细胞因子诱导的损伤可能导致朗格汉斯胰岛胰岛素分泌β细胞的破坏。存在相当大的争议(1)人类和大鼠胰岛对细胞因子的反应是否不同，(2)诱导一氧化氮形成介导细胞因子损伤的程度，以及(3)一氧化氮对胰岛的影响是否可以与活性氧或过氧亚硝酸盐的影响区分开来。在暴露于一氧化氮供体s -亚硝基谷胱甘肽、混合供体3- morpholinosydnon亚胺、次黄嘌呤/黄嘌呤氧化酶、过氧亚硝酸盐和联合细胞因子（白细胞介素-1 β、肿瘤坏死因子α和干扰素γ） 48小时后，我们平行分析了大鼠和人的胰岛反应。每个实验记录胰岛素分泌对葡萄糖的反应、胰岛素含量、DNA链断裂和早至晚期细胞凋亡。s -亚硝基谷胱甘肽或联合细胞因子可使大鼠胰岛胰岛素分泌减少，而过氧亚硝酸盐或次黄嘌呤/黄嘌呤氧化酶可使大鼠胰岛胰岛素分泌增加。对人胰岛胰岛素分泌的影响较小；细胞因子和s -亚硝基谷胱甘肽降低胰岛素含量。在所有治疗后，大鼠和人的胰岛都显示出显著且相似的DNA损伤水平。新生大鼠胰岛细胞凋亡在各处理下均有增加，但在成年大鼠或人胰岛细胞凋亡率较低，仅在细胞因子处理人胰岛时才有显著意义。所有细胞因子反应均被精氨酸类似物阻断。我们得出结论：(i)大鼠胰岛的活性氧增加，一氧化氮降低胰岛素分泌反应性。（ii）物种差异主要在于对细胞因子的反应，与大多数人类胰岛研究相比，使用的剂量较低，时间较短。（iii）细胞因子效应由一氧化氮驱动；活性氧和过氧亚硝酸盐都不能复制细胞因子的作用。（iv）大鼠和人的胰岛对DNA损伤的易感性相同。(v)细胞凋亡不是成人胰岛的首选死亡途径。（六）我们没有发现任何证据表明人类供体对这些治疗的反应模式有差异。
Cytokine-induced damage may contribute to destruction of insulin-secreting beta-cells in islets of Langerhans during autoimmune diabetes. There is considerable controversy (i) whether human and rat islets respond differently to cytokines, (ii) the extent to which cytokine damage is mediated by induction of nitric oxide formation, and (iii) whether the effects of nitric oxide on islets can be distinguished from those of reactive oxygen species or peroxynitrite. We have analyzed rat and human islet responses in parallel, 48 h after exposure to the nitric oxide donor S-nitrosoglutathione, the mixed donor 3-morpholinosydnonimine, hypoxanthine/xanthine oxidase, peroxynitrite, and combined cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma). Insulin secretory response to glucose, insulin content, DNA strand breakage, and early-to-late stage apoptosis were recorded in each experiment. Rat islet insulin secretion was reduced by S-nitrosoglutathione or combined cytokines, but unexpectedly increased by peroxynitrite or hypoxanthine/xanthine oxidase. Effects on human islet insulin secretion were small; cytokines and S-nitrosoglutathione decreased insulin content. Both rat and human islets showed significant and similar levels of DNA damage following all treatments. Apoptosis in neonatal rat islets was increased by every treatment, but was at a low rate in adult rat or human islets and only achieved significance with cytokine treatment of human islets. All cytokine responses were blocked by an arginine analogue. We conclude: (i) Reactive oxygen species increased and nitric oxide decreased insulin secretory responsiveness in rat islets. (ii) Species differences lie mainly in responses to cytokines, applied at a lower dose and shorter time than in most studies of human islets. (iii) Cytokine effects were nitric oxide driven; neither reactive oxygen species nor peroxynitrite reproduced cytokine effects. (iv) Rat and human islets showed equal susceptibility to DNA damage. (v) Apoptosis was not the preferred death pathway in adult islets. (vi) We have found no evidence of human donor variation in the pattern of response to these treatments.
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DOI：
10.1016/s0021-9258(18)54642-1
发表时间：
1991-11
期刊：
The Journal of biological chemistry
影响因子：
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作者：
J. A. Corbett;Jack R. Lancaster;M. Sweetland;M. L. McDaniel
通讯作者：
J. A. Corbett;Jack R. Lancaster;M. Sweetland;M. L. McDaniel
DOI：
10.1073/pnas.90.5.1731
发表时间：
1993-03-01
影响因子：
11.1
作者：
CORBETT, JA;SWEETLAND, MA;MCDANIEL, ML
通讯作者：
MCDANIEL, ML
DOI：
10.1016/0027-5107(91)90157-j
发表时间：
1991-09-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
AMES, BN;GOLD, LS
通讯作者：
GOLD, LS
细胞因子对胰岛β细胞的细胞毒性作用：类二十烷酸参与的证据。
影响因子：
4.8
作者：
Rabinovitch,A;Baquerizo,H;Sumoski,W
通讯作者：
Sumoski,W
β 细胞的功能状态调节 IL-1 和 TNF 诱导的细胞毒性。
DOI：
--
发表时间：
1993
期刊：
Lymphokine and cytokine research
影响因子：
--
作者：
Mehta,V;Hao,W;Brooks-Worrell,BM;Palmer,JP
通讯作者：
Palmer,JP