Nitric oxide, superoxide, and peroxynitrite effects on the insulin secretion and viability of βTC3 cells
Nitric oxide, superoxide, and peroxynitrite effects on the insulin secretion and viability of βTC3 cells
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DOI：
10.1114/1.258
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发表时间：
2000-01-01
影响因子：
3.8
通讯作者：
Lewis, RS
中科院分区：
文献类型：
--
作者：
Kavdia, M;Stanfield, JL;Lewis, RS
胰岛素依赖型糖尿病（IDDM）的发病通常与巨噬细胞浸润胰腺细胞有关。一旦激活，巨噬细胞释放一氧化氮（NO）和超氧化物（O-2（-））。这些物质或其活性中间体可能具有细胞毒性、致突变性或致癌性。先前的研究已经报道了细胞外产生的NO对胰腺细胞的胰岛素分泌和活力的正面和负面影响。先前几项评估NO对胰岛素分泌影响的研究的固有问题包括不稳定状态NO浓度暴露和其他潜在破坏性物质的产生。在这项研究中，这些问题被消除，通过使用一个修改后的实验系统，其中NO的交付是通过扩散通过透气管和O-2（-）的交付是使用酶促反应保持。释放速率是恒定的，导致实验系统中NO和O-2（-）的稳态浓度。基于反应动力学，一个模型来预测NO，O-2（-），和过氧亚硝酸根（ONOO-）的浓度在实验过程中。这项研究表明，NO、O-2（-）和ONOO-在预测浓度分别高达2.8 μ M、0.25 μ M和0.1 nM时，在短时间内不会影响β TC 3胰腺细胞的胰岛素分泌速率。(C)2000生物医学工程学会。【S0090-6964（00）00301-0】。
The onset of insulin-dependent diabetes mellitus (IDDM) is often associated with the infiltration of pancreatic cells by macrophages. Upon activation, macrophages release nitric oxide (NO) and superoxide (O-2(-)). These species or their reactive intermediates can be cytoxic, mutagenic, or carcinogenic. Previous studies have reported both positive and negative effects of extracellularly generated NO on insulin secretion and viability of pancreatic cells. Inherent problems of several previous studies assessing the effects of NO on insulin secretion include unsteady state NO concentration exposures and the generation of other potentially damaging species. In this study, these problems were eliminated by using a modified experimental system in which NO delivery was achieved via diffusion across a gas-permeable tube and O-2(-) delivery was maintained using an enzymatic reaction. The delivery rates were constant, leading to steady state concentrations of NO and O-2(-) in the experimental system. Based on reaction kinetics, a model was developed to predict NO, O-2(-), and peroxynitrite (ONOO-) concentrations during the experiment. This study showed that NO, O-2(-), and ONOO- at predicted concentrations as high as 2.8 mu M, 0.25 mu M, and 0.1 nM, respectively, do not affect the insulin secretion rates of beta TC3 pancreatic cells over short times. (C) 2000 Biomedical Engineering Society. [S0090-6964(00)00301-0].