*3.3.1 Signal proteins involved in the implementation of apoptosis of pancreatic b-cells*

When apoptosis is induced by cytokines produced by T-helpers and macrophages, the death of b-cells can be mediated by signaling systems associated with ceramides or with mitogen-activated protein kinases (MAPK). The combination of the cytokines TNF-a, IL-1b, and IFN-γ has been shown to induce beta cell death in vitro [5]. Cell death is induced by activation of the transcription factors JNK (c-Jun N-terminal kinase), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and STAT-1 (Signal Transducers and Activators of Transcription), which induce iNOS transcription. and subsequent production of the free radical NO. Inactivation of the JNK pathway makes b-cells less susceptible to IL-1-mediated death through a NO-independent process [47, 48]. Other components of the MAPK signaling pathway, p38 and ERK1/2 (extracellular signal-regulated kinase1/2), also play a possible role in cytokine-induced b-cell death [49, 50].
