Apoptosis of pancreatic β-cells in Type 1 diabetes

Authors

  • Tatsuo Tomita Departments of Integrative Bioscience and Pathology, Oregon Health and Science University, Portland, Oregon, USA

DOI:

https://doi.org/10.17305/bjbms.2017.1961

Keywords:

Apoptosis, autoimmunity, β-cells, Bcl family, caspases, cytokines, insulitis, Type 1 diabetes

Abstract

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.

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Author Biography

  • Tatsuo Tomita, Departments of Integrative Bioscience and Pathology, Oregon Health and Science University, Portland, Oregon, USA
    Departments of Integrative Bioscience and Pathology

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Apoptosis of pancreatic β-cells in Type 1 diabetes

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20-08-2017

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Apoptosis of pancreatic β-cells in Type 1 diabetes. Biomol Biomed [Internet]. 2017 Aug. 20 [cited 2024 Dec. 4];17(3):183-9. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/1961