Figure 1. The β cell-centric model of T1D pathogenesis. The model proposes that sustained systemic inflammation arising from environmental factors (e.g., viral infections, gut microbiome, diet) leads to development of ER stress in β cells. Irremediable ER stress, as a result of failed compensatory responses by ATF6 and sXBP1, leads to the dysfunction and death of β cells. The subsequent release of β-cell antigens and endogenous neoantigens triggers secondary autoimmunity. A vicious cycle then ensues, leading to destruction of β-cell mass and development of T1D. The figure shows the potential stages in pathogenesis where intervention with TUDCA might allow for ER stress remediation.