ATF4 and diabetes mellitus: It is of interest to note that ATF4 plays a central role in handling ER stress induced by amino acid imbalance (Harding et al., 2003; Kilberg et al., 2009), and accumulating evidence indicates that ER stress pathways couple obesity to other metabolic dysfunctions such as diabetes (Ozcan et al., 2004; Scheuner and Kaufman, 2008), suggesting that ATF4 may regulate lipid and carbohydrate metabolism.