These data demonstrate that, unlike pharmacological ER-stress inducers such as tunicamycin or thapsigargin, which can activate all three major pathways of the UPR, hyperglycaemia selectively impairs nuclear translocation of sXBP1 while activating the ATF6 and CHOP branches of the UPR in DN. The gene discussed is DDIT3; the disease is Hyperglycemia.