CASP8 and diabetes mellitus: Furthermore, some studies have postulated that chronic hyperglycemia stimulates pro-apoptotic pathways in pancreatic β-cells by activation of DR5/ caspase-8/3, which culminates in apoptosis of pancreatic β-cells, which further results in hyperglycemia-induced pro-apoptotic pathway and initiation of the vicious cycle of pancreatic β-cell degeneration and progression of DM.