INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles-Merieux Lyon-Sud medical Universities, 69003 Lyon, France; Endocrinology, diabetology and nutrition service, Lyon-Sud Hospital, Hospices Civils de Lyon, 69310 Pierre-Bénite, France.
Diabetes Metab. 2015 Nov;41(5):358-68. doi: 10.1016/j.diabet.2015.02.006. Epub 2015 Mar 19.
Mitochondria and the endoplasmic reticulum (ER) regulate numerous cellular processes, and are critical contributors to cellular and whole-body homoeostasis. More important, mitochondrial dysfunction and ER stress are both closely associated with hepatic and skeletal muscle insulin resistance, thereby playing crucial roles in altered glucose homoeostasis in type 2 diabetes mellitus (T2DM). The accumulated evidence also suggests a potential interrelationship between alterations in both types of organelles, as mitochondrial dysfunction could participate in activation of the unfolded protein response, whereas ER stress could influence mitochondrial function. The fact that mitochondria and the ER are physically and functionally interconnected via mitochondria-associated membranes (MAMs) supports their interrelated roles in the pathophysiology of T2DM. However, the mechanisms that coordinate the interplay between mitochondrial dysfunction and ER stress, and its relevance to the control of glucose homoeostasis, are still unknown. This review evaluates the involvement of mitochondria and ER independently in the development of peripheral insulin resistance, as well as their potential roles in the disruption of organelle crosstalk at MAM interfaces in the alteration of insulin signalling.
线粒体和内质网（ER）调节许多细胞过程，是细胞和全身内稳态的重要贡献者。更重要的是，线粒体功能障碍和 ER 应激都与肝和骨骼肌胰岛素抵抗密切相关，因此在 2 型糖尿病（T2DM）中改变葡萄糖稳态中起关键作用。累积的证据还表明这两种细胞器之间存在潜在的相互关系，因为线粒体功能障碍可能参与未折叠蛋白反应的激活，而 ER 应激可能影响线粒体功能。线粒体和 ER 通过线粒体相关膜（MAMs）在物理和功能上相互连接的事实支持它们在 T2DM 病理生理学中的相互关联作用。然而，协调线粒体功能障碍和 ER 应激之间相互作用的机制，以及其与葡萄糖稳态控制的相关性，仍然未知。这篇综述评估了线粒体和 ER 独立参与外周胰岛素抵抗的发展，以及它们在改变胰岛素信号时破坏 MAM 界面细胞器串扰中的潜在作用。
