β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes
β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes
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DOI：
10.2337/diabetes.53.2007.s119
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发表时间：
2004-02-01
期刊：
影响因子：
7.7
通讯作者：
Poitout, V
中科院分区：
文献类型：
--
作者：
Robertson, RP;Harmon, J;Poitout, V
在2型糖尿病患者中经常观察到的β细胞功能的无情下降，尽管有最佳的药物管理，但已被不同地归因于葡萄糖毒性和脂毒性。前一种理论假定高血糖症是疾病的结果，是进一步损害β细胞的第二种力量。后一种理论表明，高脂血症的常见相关缺陷是β细胞功能障碍的主要原因。我们回顾了以下证据：2型糖尿病患者持续经历氧化应激，葡萄糖浓度升高会增加β细胞中活性氧的水平，胰岛具有固有的低抗氧化酶防御，抗氧化药物和抗氧化酶的过度表达可保护β细胞免受葡萄糖毒性，以及脂毒性，在某种程度上可归因于高脂血症，仅在预先存在高血糖症的情况下发生，而葡萄糖毒性可在不存在高脂血症的情况下发生。
The relentless decline in beta-cell function frequently observed in type 2 diabetic patients, despite optimal drug management, has variously been attributed to glucose toxicity and lipotoxicity. The former theory posits hyperglycemia, an outcome of the disease, as a secondary force that further damages beta-cells. The latter theory suggests that the often-associated defect of hyperlipidemia is a primary cause of beta-cell dysfunction. We review evidence that patients with type 2 diabetes continually undergo oxidative stress, that elevated glucose concentrations increase levels of reactive oxygen species in beta-cells, that islets have intrinsically low antioxidant enzyme defenses, that antioxidant drugs and overexpression of antioxidant enzymes protect beta-cells from glucose toxicity, and that lipotoxicity, to the extent it can be attributable to hyperlipidemia, occurs only in the context of preexisting hyperglycemia, whereas glucose toxicity can occur in the absence of hyperlipidemia.