Mitochondria play fundamental role in maintaining cellular metabolic homeostasis, and metabolic disorders including type 2 diabetes (T2D) have been associated with mitochondrial dysfunction. Pathophysiological mechanisms are coupled to increased production of reactive oxygen species and oxidative stress, together with reduced bioactivity/signaling of nitric oxide (NO). Novel strategies restoring these abnormalities may have therapeutic potential in order to prevent or even treat T2D and associated cardiovascular and renal co-morbidities. A diet rich in green leafy vegetables, which contains high concentrations of inorganic nitrate, has been shown to reduce the risk of T2D. To this regard research has shown that in addition to the classical NO synthase (NOS) dependent pathway, nitrate from our diet can work as an alternative precursor for NO and other bioactive nitrogen oxide species via serial reductions of nitrate (i.e. nitrate-nitrite-NO pathway). This non-conventional pathway may act as an efficient back-up system during various pathological conditions when the endogenous NOS system is compromised (e.g. acidemia, hypoxia, ischemia, aging, oxidative stress). A number of experimental studies have demonstrated protective effects of nitrate supplementation in models of obesity, metabolic syndrome and T2D. Recently, attention has been directed towards the effects of nitrate/nitrite on mitochondrial functions including beiging/browning of white adipose tissue, PGC-1α and SIRT3 dependent AMPK activation, GLUT4 translocation and mitochondrial fusion-dependent improvements in glucose homeostasis, as well as dampening of NADPH oxidase activity. In this review, we examine recent research related to the effects of bioactive nitrogen oxide species on mitochondrial function with emphasis on T2D.

中文翻译：

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硝酸盐-亚硝酸盐-NO途径在代谢性疾病（主要是2型糖尿病）中对线粒体和NADPH氧化酶功能的调节。

线粒体在维持细胞代谢稳态中起着基本作用，而包括2型糖尿病（T2D）在内的代谢疾病与线粒体功能障碍有关。病理生理机制与增加活性氧和氧化应激的产生，以及降低一氧化氮（NO）的生物活性/信号传递有关。恢复这些异常的新策略可能具有治疗潜力，以预防或什至治疗T2D以及相关的心血管和肾脏合并症。富含绿叶蔬菜的饮食（其中含有高浓度的无机硝酸盐）已被证明可以降低罹患T2D的风险。为此，研究表明，除了经典的NO合酶（NOS）依赖途径外，通过连续减少硝酸盐（即硝酸盐-亚硝酸盐-NO途径），我们饮食中的硝酸盐可以作为NO和其他生物活性氮氧化物的替代前体。当内源性NOS系统受损（例如酸血症，缺氧，局部缺血，衰老，氧化应激）时，这种非常规途径可以在各种病理状况下充当有效的备用系统。大量实验研究表明，在肥胖症，代谢综合征和T2D模型中补充硝酸盐具有保护作用。最近，注意力集中在硝酸盐/亚硝酸盐对线粒体功能的影响上，包括白色脂肪组织的变白/变褐，PGC-1α和SIRT3依赖的AMPK活化，GLUT4易位和线粒体融合依赖性的葡萄糖稳态的改善，以及抑制NADPH氧化酶的活性。在这篇综述中，我们研究了有关生物活性氮氧化物对线粒体功能的影响的最新研究，重点是T2D。