Apoptosis of pancreatic β-cells in Type 1 diabetes

Bosnian Journal of Basic Medical Sciences

Tatsuo Tomita¹ 

[1] Departments of Integrative Bioscience and Pathology, Oregon Health and Science University, Portland, Oregon, USA;

关键词: Apoptosis;    autoimmunity;    β-cells;    Bcl family;    caspases;    cytokines;   

DOI  :  10.17305/bjbms.2017.1961

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown