Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes
Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes
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DOI：
10.2337/diabetes.53.6.1412
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发表时间：
2004-06-01
期刊：
影响因子：
7.7
通讯作者：
Hesselink, MKC
中科院分区：
文献类型：
--
作者：
Schrauwen, P;Hesselink, MKC
最近的证据表明，氧化能力降低和线粒体异常是胰岛素抵抗和2型糖尿病发展的主要因素。在这篇文章中，我们将对2型糖尿病氧化能力降低、脂毒性和线粒体异常之间的相互关系提供一个综合的观点。2型糖尿病的特征是脂肪酸代谢紊乱，并伴随着非脂肪组织中脂肪酸的积累。在代谢活跃的组织中，如骨骼肌，脂肪酸容易受到所谓的氧化损伤。除了产生能量，线粒体也是活性氧的主要来源，这可能导致脂质过氧化。特别是，线粒体基质含有DNA、RNA和许多底物氧化所必需的酶，对过氧化氢诱导的氧化损伤很敏感，需要防止脂质和脂质过氧化物质的形成和积累。最近的证据表明，线粒体解偶联参与了线粒体基质对脂质诱导的线粒体损伤的保护作用。这种保护机制的紊乱可能导致2型糖尿病的发生。
Recent evidence points toward decreased oxidative capacity and mitochondrial aberrations as a major contributor to the development of insulin resistance and type 2 diabetes. In this article we will provide an integrative view on the interrelation between decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations in type 2 diabetes. Type 2 diabetes is characterized by disturbances in fatty acid metabolism and is accompanied by accumulation of fatty acids in nonadipose tissues. In metabolically active tissues, such as skeletal muscle, fatty acids are prone to so-called oxidative damage. In addition to producing energy, mitochondria are also a major source of reactive oxygen species, which can lead to lipid peroxidation. In particular, the mitochondrial matrix, which contains DNA, RNA, and numerous enzymes necessary for substrate oxidation, is sensitive to peroxide-induced oxidative damage and needs to be protected against the formation and accumulation of lipids and lipid peroxides. Recent evidence reports that mitochondrial uncoupling is involved in the protection of the mitochondrial matrix against lipid-induced mitochondrial damage. Disturbances in this protection mechanism can contribute to the development of type 2 diabetes.