Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy

Figure 2

Necroptosis: after the union of TNF-α to its receptor, the IIb complex or necrosome can be formed. This complex induces ROS production and DNA fragmentation (see text). TNF-α: tumor necrosis factor alpha; TNFR-1: tumor necrosis factor receptor 1; DD: death domain; C-FLIPs: cellular FLICE inhibitory protein; JNK: c-Jun N-terminal kinase; TRADD: tumor necrosis factor receptor type 1-associated death domain protein; TRAF2: TNF receptor-associated factor 2; RIP1: receptor-interacting protein kinase 1; RIP1: receptor-interacting protein kinase 3; ROS: reactive oxygen species; SMases: sphingomyelinase; SPH: sphingosine; GLUL: glutamate-ammonia ligase or glutamine synthetase; GLUD1: glutamate dehydrogenase; cPLA2: calcium-dependent phospholipase A2; AA: arachidonic acid; 5-LO: 5-lipoxygenase; LOOH: lypid hydroperoxides; NADP: nicotinamide adenine dinucleotide phosphate; FAD: flavin adenine dinucleotide; AIF: apoptosis-inducing factor; H2AX: histone H2A variant; CypA: cyclophilin A.