Abstract
Apoptosis of beta cells is a feature of both type 1 and type 2 diabetes as well as loss of islets after transplantation. In type 1 diabetes, beta cells are destroyed by immunological mechanisms. In type 2 diabetes abnormal levels of metabolic factors contribute to beta cell failure and subsequent apoptosis. Loss of beta cells after islet transplantation is due to many factors including the stress associated with islet isolation, primary graft non-function and allogeneic graft rejection. Irrespective of the exact mediators, highly conserved intracellular pathways of apoptosis are triggered. This review will outline the molecular mediators of beta cell apoptosis and the intracellular pathways activated.
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Abbreviations
- T1DM:
-
Type 1 diabetes mellitus
- CTL:
-
Cytotoxic T lymphocyte
- β2m:
-
β2-microglobulin
- NOD:
-
Non-obese diabetic
- TNF:
-
Tumor necrosis factor
- TNFR:
-
TNF receptor
- FasL:
-
Fas Ligand
- FADD:
-
Fas-associated death domain
- BH3:
-
Bcl-homology domain 3
- ALPS:
-
Autoimmune lymphoproliferation syndrome
- lpr :
-
Lyphoproliferation
- gld :
-
Generalized lymphoproliferative disease
- IL-1:
-
Interleukin-1
- IL-1R:
-
IL-1 receptor
- IFN:
-
Interferon
- IFNγR:
-
IFNγ receptor
- IGRP:
-
Islet-specific glucose-6-phosphatase catalytic subunit-related protein
- SOCS:
-
Suppressor of cytokine signaling
- JNK:
-
c-Jun N-terminal kinase
- NO:
-
Nitric oxide
- iNOS:
-
Inducible NO synthase
- XIAP:
-
X-linked inhibitor of apoptosis
- ROS:
-
Reactive oxygen species
- Gpx:
-
Glutathione peroxidase
- SOD:
-
Superoxide dismutase
- IBMIR:
-
Instant blood-mediated inflammatory reaction
- IAPP:
-
Islet amyloid polypeptide
- TXNIP:
-
Thioredoxin-interacting protein
- T2DM:
-
Type 2 diabetes mellitus
- CHOP:
-
C/EBP homologous protein
- ER:
-
Endoplasmic reticulum
- PERK:
-
PKR-like ER kinase
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Acknowledgments
We thank Dr. Janette Allison for critical reading of the manuscript. This work was supported by the National Health and Medical Research Council of Australia, the Juvenile Diabetes Research Foundation and the Australian Government through the Department of Health and Ageing.
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Thomas, H.E., McKenzie, M.D., Angstetra, E. et al. Beta cell apoptosis in diabetes. Apoptosis 14, 1389–1404 (2009). https://doi.org/10.1007/s10495-009-0339-5
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DOI: https://doi.org/10.1007/s10495-009-0339-5