In an Akita mouse model, a mutation in the Ins2 gene causes proinsulin misfolding and accumulation in the ER and triggers ER stress, which, in turn, leads to pancreatic β cell death and insufficient insulin secretion, and ultimately the development of diabetes, underlining the importance of the ER in both physiologic and pathologic insulin metabolism in β cells [29]. This evidence concerns the gene INS and diabetes mellitus.