ATF4 and Glucose intolerance: In contrast, it has also shown that activation of the eIF2α/ATF4 pathway by the heme‐regulated eIF2α kinase (HRI) can promote the expression of FGF21, a metabolism‐beneficial liver hormone, thereby reducing glucose intolerance in DIO mice,235 and ensuring the effects of metformin on appetite and weight loss,236, 237, 238 indicative of the ambiguous roles of PERK pathway in T2DM.