Departments of Integrative Bioscience and Pathology, Oregon Health and Science University, Portland, Oregon, USA.
Bosn J Basic Med Sci. 2017 Aug 20;17(3):183-193. doi: 10.17305/bjbms.2017.1961.
Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of pancreatic β-cells after an asymptomatic period over years. Insulitis activates antigen presenting cells, which trigger activating CD4+ helper-T cells, releasing chemokines/cytokines. Cytokines activate CD8+ cytotoxic-T cells, which lead to β-cell destruction. Apoptosis pathway consists of extrinsic (receptor-mediated) and intrinsic (mitochondria-driven) pathway. Extrinsic pathway includes Fas pathway to CD4+-CD8+ interaction, whereas intrinsic pathway includes mitochondria-driven pathway at a balance between anti-apoptotic B-cell lymphoma (Bcl)-2 and Bcl-xL and pro-apoptotic Bad, Bid, and Bik proteins. Activated cleaved caspse-3 is the converging point between extrinsic and intrinsic pathway. Apoptosis takes place only when pro-apoptotic proteins exceed anti-apoptotic proteins. Since the concordance rate of T1DM in identical twins is about 50%, environmental factors are involved in the development of T1DM, opening a door to find means to detect and prevent further development of autoimmune β-cell destruction for a therapeutic application.
1 型糖尿病（T1DM）是在数年无症状期后，由自身免疫破坏胰腺β细胞引起的。胰岛炎激活抗原呈递细胞，触发激活 CD4+辅助性 T 细胞，释放趋化因子/细胞因子。细胞因子激活 CD8+细胞毒性 T 细胞，导致β细胞破坏。细胞凋亡途径包括外在（受体介导）和内在（线粒体驱动）途径。外在途径包括 Fas 途径到 CD4+-CD8+相互作用，而内在途径包括线粒体驱动途径，在抗凋亡 B 细胞淋巴瘤（Bcl）-2 和 Bcl-xL 与促凋亡 Bad、Bid 和 Bik 蛋白之间达到平衡。活化的裂解 caspase-3 是外在途径和内在途径的交汇点。只有当促凋亡蛋白超过抗凋亡蛋白时，才会发生细胞凋亡。由于同卵双胞胎中 T1DM 的一致性率约为 50%，因此环境因素参与了 T1DM 的发展，为寻找检测和预防自身免疫性β细胞破坏进一步发展的方法以用于治疗应用开辟了一扇大门。
