CASP8 and Hyperglycemia: The decline in the secretory capacity of pancreatic β cells causes uncontrolled hyperglycemia, which further aggravates the dysregulation of Ca2+ and initiates a vicious cycle of apoptosis by activation of a pro-apoptotic complex of DR5/FADD/caspase-8 which results in the loss of pancreatic β-cell mass and progression of DM (Fig. 7).