肥胖与2型糖尿病对骨骼肌钙处理的影响:聚焦于肌浆网和线粒体

Influence of Obesity and Type 2 Diabetes on Calcium Handling by Skeletal Muscle: Spotlight on the Sarcoplasmic Reticulum and Mitochondria.

作者信息

Eshima Hiroaki

机构信息

Department of International Tourism, Nagasaki International University, Nagasaki, Japan.

出版信息

Front Physiol. 2021 Nov 2;12:758316. doi: 10.3389/fphys.2021.758316. eCollection 2021.

Abstract

Obesity and diabetes have been shown to interfere with energy metabolism and cause peripheral insulin resistance in skeletal muscle. However, recent studies have focused on the effect metabolic insult has on the loss of muscle size, strength, and physical function. Contractile dysfunction has been linked to impaired intracellular Ca concentration ([Ca]) regulation. In skeletal muscle, [Ca] homeostasis is highly regulated by Ca transport across the sarcolemma/plasma membrane, the golgi apparatus, sarcoplasmic reticulum (SR), and mitochondria. Particularly, the SR and or mitochondria play an important role in the fine-tuning of this metabolic process. Recent studies showed that obesity and insulin resistance are associated with interactions between the SR and mitochondrial networks (the dynamic tubular reticulum formed by mitochondria), suggesting that metabolic disorders alter Ca handling by these organelles. These interactions are facilitated by specific membrane proteins, including ion channels. This review considers the impact of metabolic disorders, such as obesity and type 2 diabetes, on the regulation of [Ca] in skeletal muscle. It also discusses the mechanisms by which this occurs, focusing chiefly on the SR and mitochondria networks. A deeper understanding of the effect of metabolic disorders on calcium handling might be useful for therapeutic strategies.

摘要

肥胖和糖尿病已被证明会干扰能量代谢,并导致骨骼肌出现外周胰岛素抵抗。然而,最近的研究集中在代谢损伤对肌肉大小、力量和身体功能丧失的影响上。收缩功能障碍与细胞内钙浓度([Ca])调节受损有关。在骨骼肌中,[Ca]稳态通过跨肌膜/质膜、高尔基体、肌浆网(SR)和线粒体的钙转运受到高度调节。特别是,SR和/或线粒体在这个代谢过程的微调中起重要作用。最近的研究表明,肥胖和胰岛素抵抗与SR和线粒体网络(由线粒体形成的动态管状网状结构)之间的相互作用有关,这表明代谢紊乱会改变这些细胞器对钙的处理。这些相互作用由包括离子通道在内的特定膜蛋白促进。本综述考虑了肥胖和2型糖尿病等代谢紊乱对骨骼肌中[Ca]调节的影响。它还讨论了这种情况发生的机制,主要关注SR和线粒体网络。更深入地了解代谢紊乱对钙处理的影响可能有助于制定治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0d9/8592904/5c5894d2bffe/fphys-12-758316-g001.jpg

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