Role of apoptosis in pancreatic beta-cell death in diabetes

Apoptosis is a physiological form of cell death that occurs during normal d evelopment, and critical mediators of this process include caspases, reacti ve oxygen species, and Ca2+. Excessive apoptosis of the pancreatic beta -ce ll has been associated with diabetes. Consequently, apoptosis research has focused on how infiltrating macrophages or cytotoxic T-cells might kill pan creatic beta -cells using cytokines or death receptor triggering. Meanwhile , the intracellular events in the target beta -cell have been largely ignor ed. Elucidation of such targets might help develop improved treatment strat egies for diabetes. This article will outline recent developments in apopto sis research, with emphasis on mechanisms that may be relevant to beta -cel l death in type 1 and type 2 diabetes. Several of the models proposed in be ta -cell killing converge on Ca2+ signaling, indicating that the pancreatic beta -cell may be an ideal system in which to carefully dissect the role o f Ca2+ during apoptosis.