INS and Alzheimer disease: Diabetic 5XFAD model reveals unfolded protein response (UPR)-associated activation of the PERK/eIF2α phosphorylation pathway (Devi et al., 2012), which is not only a key mediator of translational BACE1 upregulation in AD (Devi and Ohno, 2014; Ohno, 2014, 2018) but also suppressed by insulin application (Sullivan et al., 1999).