This was reminiscent of the findings that the PERK-deficient pancreatic β-cells exhibit severe disruption of ER-Golgi anterograde trafficking and disruption of the Golgi complex, while, paradoxically, decrease of PERK gene dosage ameliorated the progression of the Akita mouse expressing the gain-of-function insulin mutant to overt diabetes; the latter was proposed to be due to decrease degradation of the wild type insulin [64]. The gene discussed is INS; the disease is diabetes mellitus.