Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic β‐Cell Dysfunction and Senescence in Type 2 Diabetes

Abstract

An increased life span and accompanying nutritional affluency have led to a rapid increase in diseases associated with aging, such as obesity and type 2 diabetes, imposing a tremendous economic and health burden on society. Pancreatic β‐cells are crucial for controlling glucose homeostasis by properly producing and secreting the glucose‐lowering hormone insulin, and the dysfunction of β‐cells determines the outcomes for both type 1 and type 2 diabetes. As the native structure of insulin is formed within the endoplasmic reticulum (ER), ER homeostasis should be appropriately maintained to allow for the proper metabolic homeostasis and functioning of β‐ cells. Recent studies have found that cellular senescence is critically linked with cellular stresses, including ER stress, oxidative stress, and mitochondrial stress. These studies implied that β‐cell senescence is caused by ER stress and other cellular stresses and contributes to β‐cells’ dysfunction and the impairment of glucose homeostasis. This review documents and discusses the current understanding of cellular senescence, β‐cell function, ER stress, its associated signaling mechanism (unfolded protein response), and the effect of ER stress on β‐cell senescence and dysfunction.