Eghbalzadeh Kaveh, Brixius Klara, Bloch Wilhelm, Brinkmann Christian
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Germany.
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Germany.
Nitric Oxide. 2014 Feb 15;37:28-40. doi: 10.1016/j.niox.2013.12.009. Epub 2013 Dec 22.
Type 2 diabetes mellitus associated with obesity, or "diabesity", coincides with an altered nitric oxide (NO) metabolism in skeletal muscle. Three isoforms of nitric oxide synthase (NOS) exist in human skeletal muscle tissue. Both neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) are constitutively expressed under physiological conditions, producing low levels of NO, while the inducible nitric oxide synthase (iNOS) is strongly up-regulated only under pathophysiological conditions, excessively increasing NO concentrations. Due to chronic inflammation, overweight/obese type 2 diabetic patients exhibit up-regulated protein contents of iNOS and concomitant elevated amounts of NO in skeletal muscle. Low muscular NO levels are important for attaining an adequate cellular redox state--thereby maintaining metabolic integrity--while high NO levels are believed to destroy cellular components and to disturb metabolic processes, e.g., through strongly augmented posttranslational protein S-nitrosylation. Physical training with submaximal intensity has been shown to attenuate inflammatory profiles and iNOS protein contents in the long term. The present review summarizes signaling pathways which induce iNOS up-regulation under pathophysiological conditions and describes molecular mechanisms by which high NO concentrations are likely to contribute to triggering skeletal muscle insulin resistance and to reducing mitochondrial capacity during the development and progression of type 2 diabetes. Based on this information, it discusses the beneficial effects of regular physical exercise on the altered NO metabolism in the skeletal muscle of overweight/obese type 2 diabetic subjects, thus unearthing new perspectives on training strategies for this particular patient group.
与肥胖相关的2型糖尿病，即“糖尿病肥胖症”，与骨骼肌中一氧化氮（NO）代谢改变同时出现。人类骨骼肌组织中存在三种一氧化氮合酶（NOS）亚型。神经元型一氧化氮合酶（nNOS）和内皮型一氧化氮合酶（eNOS）在生理条件下均组成性表达，产生低水平的NO，而诱导型一氧化氮合酶（iNOS）仅在病理生理条件下强烈上调，使NO浓度过度增加。由于慢性炎症，超重/肥胖的2型糖尿病患者骨骼肌中iNOS的蛋白含量上调，同时NO含量升高。低水平的肌肉NO对于维持适当的细胞氧化还原状态从而保持代谢完整性很重要，而高水平的NO被认为会破坏细胞成分并干扰代谢过程，例如通过强烈增强翻译后蛋白S-亚硝基化。已表明，长期进行次最大强度的体育锻炼可减轻炎症反应和iNOS蛋白含量。本综述总结了在病理生理条件下诱导iNOS上调的信号通路，并描述了在2型糖尿病发生和发展过程中，高浓度NO可能导致骨骼肌胰岛素抵抗和线粒体功能降低的分子机制。基于这些信息，本文讨论了定期体育锻炼对超重/肥胖2型糖尿病患者骨骼肌中NO代谢改变的有益作用，从而为该特定患者群体的训练策略挖掘新的视角。
