Pennathur Subramaniam, Heinecke Jay W
Department of Medicine, University of Michigan, Ann Arbor, MI 48109-0676, USA.
Antioxid Redox Signal. 2007 Jul;9(7):955-69. doi: 10.1089/ars.2007.1595.
Obesity, metabolic syndrome, and diabetes are increasingly prevalent in Western society, and they markedly increase the risk for atherosclerotic vascular disease, the major cause of death in diabetics. Although recent evidence suggests a causal role for oxidative stress in insulin resistance, diabetes, and atherosclerosis, there is considerable controversy regarding its nature, magnitude, and underlying mechanisms. Glucose promotes glycoxidation reactions in vitro, and products of glycoxidation and lipoxidation are elevated in plasma and tissue from humans suffering from diabetes, but the exact relationships between hyperglycemia and oxidative stress are poorly understood. This review focuses on molecular mechanisms of increased oxidative stress in diabetes, the relationship of oxidant production to hyperglycemia, and the potential interaction of reactive carbonyls and lipids in oxidant generation. Using highly sensitive and specific gas chromatography-mass spectrometry, molecular signatures of specific oxidation pathways were identified in tissues of diabetic humans and animals. These studies support the hypothesis that unique reactive intermediates generated in localized microenvironments of vulnerable tissues promote diabetic damage. Therapies interrupting these reactive pathways in vascular tissue might help prevent cardiovascular disease in this high-risk population.
肥胖、代谢综合征和糖尿病在西方社会日益普遍，它们显著增加了动脉粥样硬化性血管疾病的风险，而动脉粥样硬化性血管疾病是糖尿病患者死亡的主要原因。尽管最近的证据表明氧化应激在胰岛素抵抗、糖尿病和动脉粥样硬化中起因果作用，但关于其性质、程度和潜在机制仍存在相当大的争议。葡萄糖在体外促进糖氧化反应，糖氧化和脂氧化产物在糖尿病患者的血浆和组织中升高，但高血糖与氧化应激的确切关系仍知之甚少。本综述重点关注糖尿病中氧化应激增加的分子机制、氧化剂产生与高血糖的关系以及活性羰基和脂质在氧化剂生成中的潜在相互作用。使用高灵敏度和特异性的气相色谱-质谱法，在糖尿病患者和动物的组织中鉴定出特定氧化途径的分子特征。这些研究支持这样一种假说，即在易损组织的局部微环境中产生的独特反应中间体促进了糖尿病损伤。阻断血管组织中这些反应途径的疗法可能有助于预防这一高危人群的心血管疾病。
