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1 型糖尿病患者骨骼肌线粒体生物能量学的性别二态性。

Sexual dimorphism in human skeletal muscle mitochondrial bioenergetics in response to type 1 diabetes.

机构信息

Department of Pathology and Molecular Medicine, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada.

School of Kinesiology and Health Sciences, Muscle Health Research Centre, York University, Toronto, Ontario, Canada.

出版信息

Am J Physiol Endocrinol Metab. 2020 Jan 1;318(1):E44-E51. doi: 10.1152/ajpendo.00411.2019. Epub 2019 Dec 3.

Abstract

Sexual dimorphism in mitochondrial respiratory function has been reported in young women and men without diabetes, which may have important implications for exercise. The purpose of this study was to determine if sexual dimorphism exists in skeletal muscle mitochondrial bioenergetics in people with type 1 diabetes (T1D). A resting muscle microbiopsy was obtained from women and men with T1D ( = 10/8, respectively) and without T1D (control; = 8/7, respectively). High-resolution respirometry and spectrofluorometry were used to measure mitochondrial respiratory function, hydrogen peroxide (mHO) emission and calcium retention capacity (mCRC) in permeabilized myofiber bundles. The impact of T1D on mitochondrial bioenergetics between sexes was interrogated by comparing the change between women and men with T1D relative to the average values of their respective sex-matched controls (i.e., delta). These aforementioned analyses revealed that men with T1D have increased skeletal muscle mitochondrial complex I sensitivity but reduced complex II sensitivity and capacity in comparison to women with T1D. mHO emission was lower in women compared with men with T1D at the level of complex I (succinate driven), whereas mCRC and mitochondrial protein content remained similar between sexes. In conclusion, women and men with T1D exhibit differential responses in skeletal muscle mitochondrial bioenergetics. Although larger cohort studies are certainly required, these early findings nonetheless highlight the importance of considering sex as a variable in the care and treatment of people with T1D (e.g., benefits of different exercise prescriptions).

摘要

已有研究表明,在无糖尿病的年轻女性和男性中,线粒体呼吸功能存在性别二态性,这可能对运动具有重要意义。本研究旨在确定 1 型糖尿病(T1D)患者的骨骼肌线粒体生物能量是否存在性别二态性。从 T1D 患者(女性和男性分别为 10 例和 8 例)和无 T1D 患者(对照组;女性和男性分别为 8 例和 7 例)中获取静息状态下的肌肉微生物活检。使用高分辨率呼吸测量法和荧光光谱法测量线粒体呼吸功能、氢过氧化物(mHO)排放和钙保留能力(mCRC)在肌纤维束的通透性。通过比较 T1D 对女性和男性的影响,来探究 T1D 对线粒体生物能量的影响,即将 T1D 患者的女性和男性与各自性别匹配的对照组的平均值进行比较(即 delta)。上述分析表明,与 T1D 女性相比,T1D 男性的骨骼肌线粒体复合物 I 敏感性增加,但复合物 II 敏感性和能力降低。与 T1D 男性相比,T1D 女性在复合物 I 水平(琥珀酸驱动)的 mHO 排放较低,而 mCRC 和线粒体蛋白含量在性别之间保持相似。总之,T1D 女性和男性的骨骼肌线粒体生物能量表现出不同的反应。尽管需要进行更大规模的队列研究,但这些早期发现仍然强调了将性别视为 T1D 患者护理和治疗中一个变量的重要性(例如,不同运动处方的益处)。

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