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Redox Biol：二甲双胍药物和其他双胍药物作用和毒性对比

2017-09-27 Emma MedSci原创

含胍药物线粒体毒性
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许多含胍类的药物都具有抗高血糖作用，但除二甲双胍外大多表现出较强的毒性。

许多含胍类的药物都具有抗高血糖作用，但除二甲双胍外大多表现出较强的毒性。因此研究人员通过这些药物对细胞氧消耗，糖原异常基因调控，信号传导和葡萄糖生成的影响，调查二甲双胍和其他含胍药物的作用差异及其中的作用机制。

原代肝细胞和H4IIE肝癌细胞中，抗高血糖双胍DG5-DG10和苯乙双胍比二甲双胍在细胞信号传导反应、糖异生启动子表达、肝细胞葡萄糖产生的效力高达1000倍，这几种药物抑制细胞氧消耗类似，但在其他方面有显著差异。除了二甲双胍的其他双胍，抑制腺苷中的NADH氧化，指示复合物I抑制，这与通过WST-1测量的活细胞中脱氢酶活性密切相关。在分离的线粒体中，二甲双胍DG8能够使NADH / NAD +偶联随时间变化而更加降低，进而导致线粒体变性，表明DG8能直接抑制复合物I，并且具有线粒体毒性，这与上述发现一致。相比之下，二甲双胍能够选择性诱导复合物I状态来抑制能量转导，此区域氧化还原和质子转移结构域不再有效偶联，二甲双胍对线粒体NADH/NAD +偶联进行选择性氧化，不引发线粒体退化。

该研究调查了二甲双胍和其他含胍药物的差异以及其中的作用机制，为药物的进一步开发提供了重要参考。

原始出处：
Cameron AR, et al. Metformin selectively targets redox control of complex I energy transduction. Redox Biol. 2017 Aug 26;14:187-197. doi: 10.1016/j.redox.2017.08.018.

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    2018-04-30 12498ebem31暂无昵称

    #Biol#

    0

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    2018-07-21 马龙

    #药物作用#

    0

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    2018-06-03 sunylz

    #Bio#

    0

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    2017-10-13 1771ae4158m

    学习一下很不错

    0

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    2017-10-12 2227437833_79976374

    很好很好很好

    0

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    2017-10-04 yunger

    继续充电中.谢谢分享

    0

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    2017-09-29 戒馋，懒，贪

    谢谢分享.学习了

    0

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    2017-09-29 sunfeifeiyang

    血糖治疗作用机制

    0

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    2017-09-28 186****0580(小山羊）

    学习了谢谢了

    0