Although mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and disrupted lipid and calcium (Ca2+) 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 Ca2+ 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.
Keywords: Calcium homeostasis; Endoplasmic reticulum (ER); Glucose homeostasis; Insulin resistance; Mitochondria; Mitochondria-associated membranes (MAM); Organelle communication; Type 2 diabetes mellitus (T2DM); β-Cell dysfunction.