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

  1. Fumihiko Urano
  1. 1Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts
  2. 2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
  1. Corresponding author: Fumihiko Urano, fumihiko.urano{at}umassmed.edu.

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 (15). 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 (69). 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.

ER stress as a trigger for β-cell dysfunction in 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 …

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