Executioners of apoptosis in pancreatic {beta}-cells: not just for cell death.

Pancreatic beta-cell mass is dynamic and is regulated by beta-cell proliferation, neogenesis, and apoptosis. Under physiological conditions, apoptosis is tightly regulated with a slow, net rise in beta-cell mass over time. Excessive beta-cell apoptosis is an important contributor to both type 1 and type 2 diabetes development. Therefore, much effort has been given recently to better understand the mechanisms of apoptosis that occur both during physiological homeostasis and during the course of both types of diabetes. Caspases are the executioners of apoptosis that ultimately result in cell suicide. In mammals, there are 14 caspases, of which many participate in the apoptotic pathways. Genetic mouse models have been important tools for elucidation of the specific apoptotic pathways that play an essential role in beta-cell apoptosis under physiological and pathological conditions. This review focuses on the diverse roles of each of the specific caspases and their regulators, unveiling both the classical apoptotic roles as well as emerging nonapoptotic roles.