Abstract
Pancreatic islet β-cell death occurs in type 1 and 2 diabetes mellitus, leading to absolute or relative insulin deficiency. β-cell death in type 1 diabetes is due predominantly to autoimmunity. In type 2 diabetes β-cell death occurs as the combined consequence of increased circulating glucose and saturated fatty acids together with adipocyte secreted factors and chronic activation of the innate immune system. In both diabetes types intra-islet inflammatory mediators seem to trigger a final common pathway leading to β-cell apoptosis. Therefore anti-inflammatory therapeutic approaches designed to block β-cell apoptosis could be a significant new development in type 1 and 2 diabetes.
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Abbreviations
- DD :
-
Death domain
- ECSIT :
-
Evolutionary conserved signaling intermediate in Toll/IL-1 pathways
- ER :
-
Endoplasmic reticulum
- ERK :
-
Extracellular signal-regulated kinase
- FADD :
-
Fas-associated death domain
- FasL :
-
Fas ligand
- FFA :
-
Free fatty acid
- FLIP :
-
Fas-associated death domain-like IL-1β converting enzyme inhibitory protein
- IFN :
-
Interferon
- IKK :
-
IκB kinase
- IL :
-
Interleukin
- IL-1R1 :
-
IL-1 type 1 receptor
- IL-1Ra :
-
IL-1 receptor antagonist
- iNOS :
-
Inducible nitric oxide synthase
- IRAK :
-
IL-1R activated kinase
- IRF :
-
Interferon regulatory factor
- IκB :
-
Inhibitory κB protein
- JAK :
-
Janus tyrosine kinases
- JNK :
-
c-jun N-terminal kinase
- MAP :
-
Mitogen-activated protein
- MAPK :
-
Mitogen-activated protein kinase
- MEKK :
-
MAPK/ERK kinase kinase
- MORT :
-
Mediator of receptor induced toxicity
- NF :
-
Nuclear transcription factor
- NOD :
-
Nonobese diabetic
- Pdx :
-
Pancreatic duodenal homeobox factor
- PKC :
-
Protein kinase C
- ROS :
-
Reactive oxygen species
- SAPK :
-
Stress-activated protein kinases
- SERCA :
-
Sarco-/endoplasmic reticulum Ca2+ ATPase
- STAT :
-
Signal transducer and activator of transcription
- TAK :
-
Transforming growth factor β-activated kinase
- TNF :
-
Tumor necrosis factor
- TRADD :
-
TNF receptor associated death domain
- TRAF :
-
TNF receptor associated factor
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Acknowledgements
This work was supported in part by the Juvenile Diabetes Research Foundation International Grant # 4-2002-457, the Danish Diabetes Association and Novo Nordisk (J.S., T.M.P.) and by the Swiss National Science Foundation Grants #3200-067049.01 and PP00B-68874/1 and by the Max Cloetta Foundation (M.Y.D.).
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Donath, M.Y., Størling, J., Maedler, K. et al. Inflammatory mediators and islet β-cell failure: a link between type 1 and type 2 diabetes. J Mol Med 81, 455–470 (2003). https://doi.org/10.1007/s00109-003-0450-y
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DOI: https://doi.org/10.1007/s00109-003-0450-y