β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances
Abstract
:1. Introduction
2. Understanding β-Cell Death in the Pathogenesis of Diabetes Mellitus
2.1. Early Observations of Insulin Deficiency as a Driver of Hyperglycemia in Diabetes
2.2. Observations of β-Cell Loss in Human Diabetes
2.2.1. β-Cell Loss in T1D
2.2.2. β-Cell Loss in T2D
2.3. Loss of β-Cell Function in Human Diabetes
2.3.1. β-Cell Dysfunction in T1D
2.3.2. β-Cell Dysfunction in T2D
2.4. Observations of β-Cell Death in Human Diabetes
2.4.1. Evidence for β-Cell Death in Human T1D
2.4.2. Evidence for β-Cell Death in Human T2D
2.4.3. Considerations for Quantifying β-Cell Death in Human Diabetes
3. Advances in Understanding the Mechanisms of β-Cell Death in Diabetes
3.1. Autoimmune-Associated β-Cell Death in T1D
3.1.1. The Immune System in T1D-Associated β-Cell Death
3.1.2. The β-Cell in T1D-Associated β-Cell Death
3.2. Islet Amyloid-Induced β-Cell Death in T2D
3.3. Mechanisms of Proinflammatory Cytokine-Induced β-Cell Death
3.3.1. IL-1β Signaling in β-Cell Death
3.3.2. TNFα Signaling in β-Cell Death
3.3.3. IFNγ and IFNα Signaling in β-Cell Death
3.4. Endoplasmic Reticulum Stress-Induced β-Cell Death
3.4.1. ER Stress-Induced β-Cell Death in Models of T2D
3.4.2. ER Stress-Induced β-Cell Death in Models of T1D
3.5. Oxidative-Stress-Induced β-Cell Death
3.6. Glucotoxicity and Lipotoxicity in β-Cell Death
4. Potential Future Advances in Understanding β-Cell Death in Diabetes
4.1. Evidence for β-Cell Apoptosis, Necrosis, and Regulated Necrosis
4.1.1. β-Cell Apoptosis
4.1.2. β-Cell Necrosis
4.1.3. β-Cell Regulated Necrosis
4.2. Differentiating between Forms of β-Cell Death
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mukherjee, N.; Lin, L.; Contreras, C.J.; Templin, A.T. β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances. Metabolites 2021, 11, 796. https://doi.org/10.3390/metabo11110796
Mukherjee N, Lin L, Contreras CJ, Templin AT. β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances. Metabolites. 2021; 11(11):796. https://doi.org/10.3390/metabo11110796
Chicago/Turabian StyleMukherjee, Noyonika, Li Lin, Christopher J. Contreras, and Andrew T. Templin. 2021. "β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances" Metabolites 11, no. 11: 796. https://doi.org/10.3390/metabo11110796