β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances

• Published in: Metabolites Vol. 11; no. 11; p. 796
• Main Authors: Mukherjee, Noyonika, Lin, Li, Contreras, Christopher J, Templin, Andrew T
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.11.2021; MDPI
• Subjects: Amyloid; Animal models; Apoptosis; Autopsies; Beta cells; Cell death; Chronic illnesses; Cytokines; cytotoxicity; Diabetes; diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Disease; Glucose; Hyperglycemia; Inflammation; Insulin; Insulin resistance; Insulin secretion; islet; Lymphocytes T; Molecular modelling; Oxidative stress; Pancreas; Pathogenesis; Review; Reviews; Volumetric analysis; β cell; β cell; diabetes mellitus; cell death; islet; cytotoxicity
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo11110796

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.