Intertwined role of reactive oxygen, nitrogen and carbon in diabetic state
Intertwined role of reactive oxygen, nitrogen and carbon in diabetic state
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DOI：
10.15406/mojcsr.2015.02.00030
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
S. Venugopal
中科院分区：
文献类型：
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作者：
S. Venugopal
糖尿病是多种病因的代谢紊乱，其特征在于由胰岛素分泌或胰岛素作用或两者的缺陷引起的慢性高血糖症。在糖尿病患者中，特别是在血糖控制不佳的患者中，活性氧（ROS）和脂质过氧化反应的产生增加。活性氧（ROS）或活性羰基（RCS）的稳态水平的增加可分别导致所谓的“氧化应激”或“羰基应激”。活性氮物质（RNS）也是ROS的一个子集。ROS和RNS包括羟基自由基（· OH）、过氧化氢（H2O2）、超氧化物（O2 ·）、一氧化氮（NO·）、过氧亚硝酸根（ONOO−）。在生理条件下，线粒体是细胞内ROS产生的主要场所，这是由于电子沿着呼吸链沿着泄漏。蛋白激酶C在高血糖条件下也在视网膜内皮细胞中被激活，并可导致NADH氧化酶的激活。金属催化还原性碳水化合物的自动氧化可能参与AGEs和ROS的形成。己糖胺生物合成途径是葡萄糖代谢的另一条途径，它可能介导葡萄糖的一些毒性作用。氧化脂蛋白激活炎症信号，进而加重炎症。因此，清除氧化和亚硝化应激以及抑制炎症被认为是治疗糖尿病并发症的良好策略。
Diabetes is a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia caused by defects in the secretion of insulin or the action of insulin, or both. Production of reactive oxygen species (ROS) and lipid peroxidation are increased in diabetic patients, especially in those with poor glycemic control. An increase in steady-state level of reactive oxygen species (ROS) or reactive carbonyl species (RCS) may result in so-called “oxidative stress” or “carbonyl stress”, respectively. Reactive nitrogen species (RNS) is also a subset of ROS. ROS and RNS include hydroxyl radical ( • OH), hydrogen peroxide (H2O2), superoxide (O2 •), nitric oxide (NO•), peroxynitrite (ONOO−). In physiological conditions, mitochondria are the major site of intracellular ROS production, due to electron leakage along the respiratory chain. Protein kinase C also becomes activated in retinal endothelial cells under hyperglycemic conditions and can lead to activation of NADH oxidase. Metal-catalyzed auto oxidation of reducing carbohydrates could be involved in the formation of AGEs and ROS. Hexosamine biosynthesis pathway is an additional pathway of glucose metabolism that may mediate some of the toxic effects of glucose Oxidized lipoproteins activate inflammatory signaling, which in turn aggravates the inflammation. Therefore, clearance of oxidative and nitrosative stress and inhibition of inflammation have been considered good strategies for the treatment of diabetic complications.