Department of Molecular and Cellular Endocrinology, City of Hope Beckman Research Institute, Duarte, California, USA.
The Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, California, USA.
Compr Physiol. 2020 Jul 8;10(3):785-809. doi: 10.1002/cphy.c190029.
The skeletal muscle is the largest organ in the body, by mass. It is also the regulator of glucose homeostasis, responsible for 80% of postprandial glucose uptake from the circulation. Skeletal muscle is essential for metabolism, both for its role in glucose uptake and its importance in exercise and metabolic disease. In this article, we give an overview of the importance of skeletal muscle in metabolism, describing its role in glucose uptake and the diseases that are associated with skeletal muscle metabolic dysregulation. We focus on the role of skeletal muscle in peripheral insulin resistance and the potential for skeletal muscle-targeted therapeutics to combat insulin resistance and diabetes, as well as other metabolic diseases like aging and obesity. In particular, we outline the possibilities and pitfalls of the quest for exercise mimetics, which are intended to target the molecular mechanisms underlying the beneficial effects of exercise on metabolic disease. We also provide a description of the molecular mechanisms that regulate skeletal muscle glucose uptake, including a focus on the SNARE proteins, which are essential regulators of glucose transport into the skeletal muscle. © 2020 American Physiological Society. Compr Physiol 10:785-809, 2020.
骨骼肌是人体最大的器官，按质量计算。它也是葡萄糖内稳态的调节剂，负责从循环中摄取 80%的餐后葡萄糖。骨骼肌对代谢至关重要，既是葡萄糖摄取的作用，也是运动和代谢疾病的重要作用。在本文中，我们概述了骨骼肌在代谢中的重要性，描述了它在葡萄糖摄取中的作用以及与骨骼肌代谢失调相关的疾病。我们重点介绍了骨骼肌在周围胰岛素抵抗中的作用，以及骨骼肌靶向治疗在对抗胰岛素抵抗和糖尿病以及衰老和肥胖等其他代谢疾病方面的潜力。特别是，我们概述了寻找运动模拟物的可能性和陷阱，这些模拟物旨在针对运动对代谢疾病有益影响的分子机制。我们还描述了调节骨骼肌葡萄糖摄取的分子机制，重点介绍了 SNARE 蛋白，它们是葡萄糖向骨骼肌转运的必需调节剂。© 2020 美国生理学会。综合生理学 10:785-809,2020。
