β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances
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Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Lilly Diabetes Center of Excellence, Indiana Biosciences Research Institute, Indianapolis, IN 46202, USA
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Department of Medicine, Roudebush Veterans Affairs Medical Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
4
Center for Diabetes and Metabolic Diseases, School of Medicine, Indiana University, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Dawn Belt Davis and Raghavendra G. Mirmira
Metabolites 2021, 11(11), 796; https://doi.org/10.3390/metabo11110796
Received: 12 October 2021
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Revised: 15 November 2021
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Accepted: 18 November 2021
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Published: 22 November 2021
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
β-cell death is regarded as a major event driving loss of insulin secretion and hyperglycemia in both type 1 and type 2 diabetes mellitus. In this review, we explore past, present, and potential future advances in our understanding of the mechanisms that promote β-cell death in diabetes, with a focus on the primary literature. We first review discoveries of insulin insufficiency, β-cell loss, and β-cell death in human diabetes. We discuss findings in humans and mouse models of diabetes related to autoimmune-associated β-cell loss and the roles of autoreactive T cells, B cells, and the β cell itself in this process. We review discoveries of the molecular mechanisms that underlie β-cell death-inducing stimuli, including proinflammatory cytokines, islet amyloid formation, ER stress, oxidative stress, glucotoxicity, and lipotoxicity. Finally, we explore recent perspectives on β-cell death in diabetes, including: (1) the role of the β cell in its own demise, (2) methods and terminology for identifying diverse mechanisms of β-cell death, and (3) whether non-canonical forms of β-cell death, such as regulated necrosis, contribute to islet inflammation and β-cell loss in diabetes. We believe new perspectives on the mechanisms of β-cell death in diabetes will provide a better understanding of this pathological process and may lead to new therapeutic strategies to protect β cells in the setting of diabetes.
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Keywords:
β cell; cell death; islet; diabetes mellitus; cytotoxicity
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MDPI and ACS Style
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
AMA Style
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
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