ER Stress as a Trigger for β-Cell Dysfunction and Autoimmunity in Type 1 Diabetes

Type 1 diabetes is an autoimmune disease characterized by the destruction of pancreatic β-cells and an absolute deficiency of insulin. Patients with type 1 diabetes are insulin dependent for life and require multiple daily insulin injections or the use of an insulin pump. It has been considered that β-cell dysfunction and death in type 1 diabetes results from a combination of inflammation, autoimmunity, β-cell stress, and insulin resistance (1–5). Clinical and experimental evidence has indicated that defects in β-cell function precede the massive death of β-cells by severe infiltration of T cells into the islets and the clinical onset of type 1 diabetes (6–9). However, the mechanisms involved in β-cell dysfunction before the onset of clinical type 1 diabetes are unclear. In this issue of Diabetes , Tersey et al. (10) add a new dimension to the progression of type 1 diabetes by demonstrating that endoplasmic reticulum (ER) stress in β-cells precedes the clinical onset of type 1 diabetes.The ER performs a number of important cellular tasks, including protein folding, calcium regulation, redox regulation, and life or death decisions (11,12). Within the β-cell, insulin production and secretion depend on the processing capacity of the …