Miro1介导2型糖尿病中的骨骼肌胰岛素抵抗。
完整摘要 · 中文译文
骨骼肌线粒体动力学失衡通过尚不完全明确的机制促进2型糖尿病（T2D）的发生和进展。在此，我们研究了线粒体Rho GTP酶1（Miro1）——一种线粒体外膜酶——在2型糖尿病（T2D）中调节骨骼肌胰岛素作用和葡萄糖稳态的作用。在一项横断面临床研究中，我们发现Miro1在肥胖和T2D患者的骨骼肌中积累，这一现象在T2D小鼠模型中得到了进一步验证。这种积累是由于胰岛素介导的AKT与Miro1在线粒体外膜上的相互作用不足所致。在一项随机对照试验（NCT02977442）中，我们发现运动训练可减轻T2D患者骨骼肌中Miro1的积累，同时改善胰岛素敏感性。肌肉特异性Miro1缺失可改善小鼠和细胞的氧化能力及胰岛素敏感性。综上所述，这些数据支持骨骼肌Miro1在T2D病理生理学中具有关键调控作用。ClinicalTrials.gov标识符：NCT02977442。
完整摘要 · 英文原文
Imbalanced skeletal muscle mitochondrial dynamics contribute to the onset and progression of type 2 diabetes (T2D) by mechanisms that remain incompletely understood. Here, we examined the role of Mitochondrial Rho GTPase 1 (Miro1), an outer mitochondrial membrane enzyme, in regulating skeletal muscle insulin action and glucose homeostasis in type 2 diabetes (T2D). In a cross-sectional clinical study, we show that Miro1 accumulates in the skeletal muscle of patients with obesity and T2D, which was further replicated in mouse models of T2D. This accumulation is explained by inadequate insulin-mediated interaction between AKT and Miro1 at the outer mitochondrial membrane. In a randomized controlled trial (NCT02977442), we show that exercise training relieves skeletal muscle Miro1 accumulation while improving insulin sensitivity in patients with T2D. Muscle-specific Miro1 deletion improves oxidative capacity and insulin sensitivity in mice and cells. Taken together, these data support a key regulatory role for skeletal muscle Miro1 in the pathophysiology of T2D. ClinicalTrials.gov Identifier: NCT02977442.