Apoptosis of pancreatic β-cells in Type 1 diabetes

Can the autoimmune β-cell destruction be prevented?

Dr. Tatsuo Tomita, principal investigator and author, is affiliated with Departments of Integrative Bioscience and Pathology, Oregon Health and Science University, Portland, Oregon, USA
Dr. Tatsuo Tomita, principal investigator and author, is affiliated with Departments of Integrative Bioscience and Pathology, Oregon Health and Science University, Portland, Oregon, USA

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.

Reference
Tomita T. Apoptosis of pancreatic β-cells in Type 1 diabetes. Bosn J Basic Med Sci. 2017 Apr 3. doi: 10.17305/bjbms.2017.1961. [Epub ahead of print]

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