Читать книгу Handbook of Diabetes - Rudy Bilous - Страница 44

One model of β cell destruction is via the process of apoptosis or programmed cell death (Figure 6.8). This is effected by the activation of cellular caspases triggered by extrinsic means, including the interaction of cell surface Fas (the death‐signalling molecule) with its ligand FasL, on the surface of infiltrating CD4 and CD8 cells. There is an intrinsic pathway mediated by a balance between anti‐ and pro‐apoptotic mitochondrial pathways and both converge via the caspase activation pathway to cause β cell death. Other factors that induce apoptosis include macrophage derived nitric oxide (NO) and toxic free radicals, and disruption of the cell membrane by perforin and granzyme B produced by cytotoxic T cells. T cell cytokines (e.g. interleukin–1, tumour necrosis factor–α, interferon–γ) have been shown to up‐regulate Fas and FasL and induce NO and toxic free radicals.