cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes
cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes
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DOI：
10.1016/j.bbrc.2008.01.017
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发表时间：
2008-03-21
影响因子：
3.1
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Mitsuishi, Masanori;Miyashita, Kazutoshi;Itoh, Hiroshi
骨骼肌线粒体功能障碍与多种病理过程有关，包括2型糖尿病的胰岛素抵抗。最近的一份报告表明，热量限制可以通过依赖一氧化氮/cGMP的途径来调节线粒体的功能。根据这些发现，我们检测了cGMP是否能挽救高糖高胰岛素诱导的C2C12肌小管细胞线粒体功能障碍。CGMP处理细胞可促进线粒体的生物合成和ATP合成，而不增加ROS的产生，同时上调参与氧化磷酸化和ROS还原的基因。线粒体膜电位降低，与卡路里限制作用相似，可逆转高糖、高胰岛素所致的线粒体功能障碍。这些结果表明，骨骼肌中增强的cGMP依赖级联反应可以减轻2型糖尿病和代谢综合征患者观察到的胰岛素抵抗。(C)2008 Elsevier Inc.保留所有权利。
Mitochondrial dysfunction in the skeletal muscle has been implicated in a wide variety of pathological processes including insulin resistance in type 2 diabetes. A recent report indicates that calorie restriction can modulate mitochondrial function through the nitric oxide/cGMP-dependent pathway. Following up on these findings, we examined whether cGMP could rescue mitochondrial dysfunction in C2C12 myotubular cells induced by conditions of high-glucose and high-insulin. Treatment of the cells with cGMP promoted mitochondrial biogenesis and ATP synthesis without enhancing production of reactive oxygen species (ROS) in association with up-regulation of the genes involved in oxidative phosphorylation and ROS reduction. The increased mitochondria were revealed to have lower membrane potential, which is similar to the effect of calorie restriction, and reversed mitochondrial dysfunction caused by high-glucose and high-insulin. These results indicated that augmented cGMP-dependent cascades in the skeletal muscle may attenuate insulin resistance observed in patients with type 2 diabetes and metabolic syndrome. (c) 2008 Elsevier Inc. All rights reserved.