Role of pancreatic β-cell death and cell death-associated inflammation in diabetes

Abstract

Pancreatic β-cell death of various types has diverse and important roles in the pathogenesis of both type 1 (T1D) and type 2 (T2D) diabetes. The most widely recognized types of β-cell death in diabetes are apoptosis (type 1 programmed cell death) and necrosis. Apoptosis of β-cells is the key and final step in the development of T1D and contributes to β-cell failure or dysfunction in T2D. In the course of natural T1D, apoptotic β-cells undergoing secondary necrosis probably due to their defective clearance by phagocytes, may be involved in the initiation and development of the disease. Recently, autophagy (type 2 programmed cell death) is proposed as a third type of cell death and is being recognized as having certain roles in the prevention and execution of β-cell death, depending on the cellular context. Moreover, as dying β-cells are routinely exposed to the immune system, β-cell death could also affect the development of diabetes through regulation of inflammation or immune response. In this review, we describe the role of various types of pancreatic β-cell death in the development of T1D and T2D. We also discuss the role of dying β-cells in the control of inflammation which contributes to the pathogenesis of diabetes.