INS and diabetes mellitus: The notion of ER stress in diabetes originated after several studies concluded that during the pre-diabetic period, β cells entered a hyper-active mode of pro-insulin synthesis, which led to an increase in protein misfolding; the mis-folded proteins eventually accumulated at the ER and caused ERS (Kaufman, 2002; Dobson, 2003; Sitia and Braakman, 2003; Thomas et al., 2011; Kim et al., 2012).