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肾上腺素受体对肌肉和脂肪组织中雷帕霉素靶蛋白的调节作用。

Adrenoceptor regulation of the mechanistic target of rapamycin in muscle and adipose tissue.

机构信息

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

出版信息

Br J Pharmacol. 2019 Jul;176(14):2433-2448. doi: 10.1111/bph.14616. Epub 2019 Apr 7.

Abstract

A vital role of adrenoceptors in metabolism and energy balance has been well documented in the heart, skeletal muscle, and adipose tissue. It has been only recently demonstrated, however, that activation of the mechanistic target of rapamycin (mTOR) makes a significant contribution to various metabolic and physiological responses to adrenoceptor agonists. mTOR exists as two distinct complexes named mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) and has been shown to play a critical role in protein synthesis, cell proliferation, hypertrophy, mitochondrial function, and glucose uptake. This review will describe the physiological significance of mTORC1 and 2 as a novel paradigm of adrenoceptor signalling in the heart, skeletal muscle, and adipose tissue. Understanding the detailed signalling cascades of adrenoceptors and how they regulate physiological responses is important for identifying new therapeutic targets and identifying novel therapeutic interventions. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.

摘要

肾上腺素受体在心脏、骨骼肌和脂肪组织的代谢和能量平衡中起着至关重要的作用,这一点在医学文献中已有充分记载。然而,最近才发现,雷帕霉素靶蛋白(mTOR)的激活对肾上腺素受体激动剂引起的各种代谢和生理反应有重要贡献。mTOR 存在两种不同的复合物,分别命名为 mTOR 复合物 1(mTORC1)和 mTOR 复合物 2(mTORC2),并已被证明在蛋白质合成、细胞增殖、肥大、线粒体功能和葡萄糖摄取中发挥关键作用。这篇综述将描述 mTORC1 和 2 在心脏、骨骼肌和脂肪组织中作为肾上腺素受体信号的新范例的生理意义。了解肾上腺素受体的详细信号通路及其如何调节生理反应对于确定新的治疗靶点和识别新的治疗干预措施非常重要。相关文章:本文是关于肾上腺素能受体——旧角色的新作用的专题的一部分。要查看该部分的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.

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