Rieusset Jennifer
Faculté de médecine Lyon-Sud, UMR INSERM U1060, CarMeN Laboratory, Lyon 1 University, INRA U1397, 165 chemin du grand Revoyet, BP12, F-69921, Oullins Cedex, France.
Adv Exp Med Biol. 2017;997:171-186. doi: 10.1007/978-981-10-4567-7_13.
Although mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and disrupted lipid and calcium (Ca) homeostasis are classically associated with both insulin resistance and β-cell dysfunction in type 2 diabetes mellitus (T2DM), the interplay between these metabolic stresses is less known. Both organelles interact through contact points known as mitochondria-associated membranes (MAM), in order to exchange both lipids and Ca and regulate cellular homeostasis. Recent evidences suggest that MAM could be an important hub for hormonal and nutrient signaling in the liver and that ER-mitochondria miscommunication could participate to hepatic insulin resistance, highlighting the importance of MAM in the control of glucose homeostasis. Here, we specifically discuss the role of MAM in hormonal and nutrient-regulated signaling pathways supporting a role in the control of glucose homeostasis and analyze the evidences pointing a role of ER-mitochondria miscommunication in T2DM. Collectively, these data suggest that targeting MAM structure and function might be a novel strategy for the treatment of T2DM.
尽管线粒体功能障碍、内质网（ER）应激以及脂质和钙（Ca）稳态破坏在2型糖尿病（T2DM）中经典地与胰岛素抵抗和β细胞功能障碍相关联，但这些代谢应激之间的相互作用却鲜为人知。这两种细胞器通过称为线粒体相关膜（MAM）的接触点相互作用，以交换脂质和Ca并调节细胞稳态。最近的证据表明，MAM可能是肝脏中激素和营养信号的重要枢纽，并且内质网-线粒体通讯失调可能参与肝脏胰岛素抵抗，突出了MAM在控制葡萄糖稳态中的重要性。在这里，我们具体讨论MAM在支持其在控制葡萄糖稳态中发挥作用的激素和营养调节信号通路中的作用，并分析指出内质网-线粒体通讯失调在T2DM中发挥作用的证据。总体而言，这些数据表明，靶向MAM的结构和功能可能是治疗T2DM的新策略。
