Considering the PERK-ATF-4-GRP-78 pathway, PERK was found to be downregulated in T2DM subjects in our study, which might be explained by the fact that, during acute or chronic gluco-lipotoxic stresses in secretory cells, pancreatic β cells, and adipocytes, in particular, excessive demand of protein synthesis arises (47). This evidence concerns the gene EIF2AK3 and type 2 diabetes mellitus.