Don´t give up on mitochondria as a target for the treatment of diabetes and its complications

In this editorial,we discuss an article by Wang et al,focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion.Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications,efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results.The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target.While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models,the results regarding glycemic control have been mixed,and no studies have evaluated their hypoglycemic effects in diabetic patients.Nonetheless,pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications.Here,we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction.We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.

线粒体靶向抗氧化剂SS-31(H-D-Arg-Dmt-Lys-Phe-NH_2)的发现及其研究进展

SS-02[Dmt^1]DALDA(H-Dmt-D-Arg-Phe-Lys-NH_2,Dmt:2,6-dimethyl-L-tyrosine)是衍生与皮啡肽的阿片肽,它具有很强的镇痛作用和良好的细胞膜通过能力,在对其进行深入的机制研究后发现了线粒体靶向抗氧化肽SS-31(H-D-Arg-Dmt-Lys-Phe-NH_2)。SS-31对缺血再灌注损伤、神经退行性疾病、心力衰竭、肌肉老化等和自由基有关的疾病具有治疗效果。本文综述了由SS-02到SS-31的发现历程及其SS-31的药理学和临床研究进展。