Robertson R Paul, Harmon Jamie, Tran Phuong Oanh T, Poitout Vincent
Pacific Northwest Research Institute and the Departments of Medicine and Pharmacology, University of Washington, Seattle, Washington 98122, USA.
Diabetes. 2004 Feb;53 Suppl 1:S119-24. doi: 10.2337/diabetes.53.2007.s119.
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.
尽管进行了最佳的药物治疗，但2型糖尿病患者中经常观察到的β细胞功能持续下降，各种因素被归因于葡萄糖毒性和脂毒性。前一种理论认为高血糖是该疾病的结果，是进一步损害β细胞的次要因素。后一种理论表明，常与之相关的高脂血症缺陷是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，升高的葡萄糖浓度会增加β细胞中活性氧的水平，胰岛本身的抗氧化酶防御能力较低，抗氧化药物和抗氧化酶的过表达可保护β细胞免受葡萄糖毒性，并且脂毒性（就其可归因于高脂血症的程度而言）仅在先前存在高血糖的情况下发生，而葡萄糖毒性可在无高脂血症的情况下发生。
