Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy
Open Access
- 19 February 2018
- journal article
- review article
- Published by Hindawi Limited in Journal of Diabetes Research
- Vol. 2018, 1-19
- https://doi.org/10.1155/2018/9601801
Abstract
Purpose of Review. Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. Recent Findings. Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus. They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. Summary. Necroptosis, autophagy, and pyroptosis are molecular mechanisms that modulate the survival of the pancreatic beta cell, demonstrating the importance of the immune system in glucolipotoxicity processes and the potential role for immunometabolism as another component of what once known as the “ominous octet.”Keywords
This publication has 177 references indexed in Scilit:
- Endoplasmic reticulum stress sensitizes pancreatic beta cells to interleukin-1β-induced apoptosis via Bim/A1 imbalanceCell Death & Disease, 2013
- Destruction of Tissue, Cells and Organelles in Type 1 Diabetic Rats Presented at Macromolecular ResolutionScientific Reports, 2013
- Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 DiabetesCells, 2013
- Risk Factors and Primary Prevention Trials for Type 1 DiabetesInternational Journal of Biological Sciences, 2013
- Autophagy and the Integrated Stress ResponseMolecular Cell, 2010
- Necroptosis as an alternative form of programmed cell deathCurrent Opinion in Cell Biology, 2010
- Endoplasmic reticulum stress in β-cells and development of diabetesCurrent Opinion in Pharmacology, 2009
- Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotesCell Death & Differentiation, 2009
- Insulin as an autoantigen in NOD/human diabetesCurrent Opinion in Immunology, 2008
- Morphological and cytochemical determination of cell death by apoptosisHistochemistry and Cell Biology, 2007