The binary switch that controls the life and death decisions of ER stressed beta cells

Abstract

Diabetes mellitus is a group of common metabolic disorders defined by hyperglycemia. One of the most important factors contributing to hyperglycemia is dysfunction and death of beta cells. Increasing experimental, clinical, and genetic evidence indicates that endoplasmic reticulum (ER) stress plays an important role in beta cell dysfunction and death during the progression of type 1 and type 2 diabetes as well as genetic forms of diabetes such as Wolfram syndrome. The mechanisms of ER stress-mediated beta cell dysfunction and death are complex and not homogenous. Here we review the recent key findings on the role of ER stress and the unfolded protein response (UPR) in beta cells and the mechanisms of ER stress-mediated beta cell dysfunction and death. Complete understanding of these mechanisms will lead to novel therapeutic modalities for diabetes.