Mitochondria as a Target for Future Diabetes Treatments

Mitochondria as a Target for Future Diabetes Treatments
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线粒体作为未来糖尿病治疗的目标

DOI：
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发表时间：
2015
期刊：
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通讯作者：
M. Szibor
M. Szibor
中科院分区：
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文献类型：
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作者：
F. Thimm;M. Szibor

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糖尿病正在迅速成为世界上最危险的连环杀手。 1 型糖尿病 (T1D) 是一种目前无法治愈的自身免疫性疾病，其特点是产生胰岛素的胰腺 β 细胞进行性、最终彻底破坏。 2 型糖尿病 (T2D) 描述了外周组织胰岛素抵抗、胰腺 β 细胞胰岛素分泌不足以及胰腺 α 细胞分泌过多胰高血糖素的组合。 T1D 以及严重的 T2D 病例均采用胰岛素替代治疗，这只能被视为疾病急性期的生命支持。产生胰岛素的胰腺β细胞的胰岛替代是胰岛素缺乏型糖尿病（T1D）和胰岛素抵抗型糖尿病（T2D）的潜在治疗方法，并且可能将糖尿病管理从挽救生命措施转变为治愈措施。胰岛移植的关键挑战之一是活性氧（ROS）的产生和相关的氧化应激，这限制了移植物的寿命。 ROS 的主要泄漏发生在线粒体电子传递链 (ETC) 的氧化磷酸化过程中。此外，高血糖诱导的超氧化物（O2•-）产生与糖尿病并发症（大血管和微血管）的发生和进展有关。糖尿病患者体内活性氧的减少可以预防长期糖尿病并发症的发生。这篇综述概述了线粒体在糖尿病中的作用，并将其作为未来糖尿病治疗的可能目标。
Diabetes mellitus is rapidly becoming the world’s most dangerous serial killer. Type 1 diabetes (T1D) is a currently incurable autoimmune disease marked by progressive, and eventually exhaustive, destruction of the insulin-producing pancreatic beta cells. Type 2 diabetes (T2D) describes the combination of insulin resistance in peripheral tissue, insufficient insulin secretion from the pancreatic beta cells, and excessive glucagon secretion from the pancreatic alpha cells. T1D as well as severe cases of T2D are treated with insulin replacement, which can merely be considered as life support for the acute phases of the disease. Islet replacement of insulin-producing pancreatic beta cells represents a potential treatment method for both insulin-depleted diabetes (T1D) and insulin-resistant diabetes (T2D) and may shift diabetes management from life saving measures to a cure. One of the key challenges in islet transplants is the generation of reactive oxygen species (ROS) and the associated oxidative stress, which restricts graft longevity. A major leak of ROS takes place during oxidative phosphorylation at mitochondrial electron transport chain (ETC). Additionally, hyperglycemia-induced superoxide (O2•-) production has been linked to the development and progression of diabetic complications, both macrovascular and microvascular. Decreasing ROS in diabetic patients may prevent the incidence of long term diabetes complications. This review provides an overview of the role of mito­chondria in diabetes, introducing them as a possible target for future treatment of diabetes.