Mechanisms of pancreatic β-cell apoptosis in diabetes and its therapies

Abstract

Diabetes occurs when β-cells no longer function properly or have been mostly destroyed. Pancreatic β-cell loss by apoptosis and other modes of death contributes to both autoimmune type 1 diabetes and type 2 diabetes. Programmed pancreatic β-cell death can be induced by multiple stresses in both major types of diabetes. There are also several rare forms of diabetes, including Wolcott-Rallison syndrome, Wolfram syndrome, as well as some forms of maturity onset diabetes of the young that are caused by mutations in genes that may play important roles in β-cell survival. The use of islet transplantation as a treatment for diabetes is also limited by excessive β-cell death. Mechanistic insights into the control of multiple modes of β-cell death are therefore important for the prevention and treatment of diabetes. Indeed, a substantial quantity of research has been dedicated to this area over the past decade. In this chapter, we will review the factors that influence the propensity of β-cells to die and the mechanisms of programmed cell death involved in the initiation and progression of diabetes.