Mechanisms of pancreatic beta-cell apoptosis in diabetes and its therapies.

Diabetes occurs when beta-cells no longer function properly or have been destroyed. Pancreatic beta-cell death by apoptosis contributes significantly in both autoimmune type 1 diabetes and type 2 diabetes. Pancreatic beta-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 beta-cell survival. The use of islet transplantation as a treatment for diabetes is also limited by excessive beta-cell apoptosis. Mechanistic insights into the control of pancreatic beta-cell apoptosis 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 review the factors that influence the propensity of beta-cells to undergo apoptosis and the mechanisms of this programmed cell death in the initiation and progression of diabetes.