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.