Signalling via the XBP1 branch of the UPR is required for an adaptive ER response in DN, while genetic disruption or functional inactivation of this pathway in murine models of type 1 diabetes mellitus (lack of insulin) and type 2 diabetes mellitus (impaired insulin signalling secondary to insulin resistance) promotes a maladaptive UPR. This evidence concerns the gene INS and type 1 diabetes mellitus.