Role of apoptosis in pancreatic β-cell death in diabetes

Apoptosis is a physiological form of cell death that occurs during normal development, and critical mediators of this process include caspases, reactive oxygen species, and Ca²⁺. Excessive apoptosis of the pancreatic β-cell has been associated with diabetes. Consequently, apoptosis research has focused on how infiltrating macrophages or cytotoxic T-cells might kill pancreatic β-cells using cytokines or death receptor triggering. Meanwhile, the intracellular events in the target β-cell have been largely ignored. Elucidation of such targets might help develop improved treatment strategies for diabetes. This article will outline recent developments in apoptosis research, with emphasis on mechanisms that may be relevant to β-cell death in type 1 and type 2 diabetes. Several of the models proposed in β-cell killing converge on Ca²⁺ signaling, indicating that the pancreatic β-cell may be an ideal system in which to carefully dissect the role of Ca²⁺ during apoptosis.