2023
DOI: 10.3389/fendo.2023.1212716
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Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies

Jeeyeon Cha,
Cristina Aguayo-Mazzucato,
Peter J. Thompson

Abstract: Cellular senescence is a response to a wide variety of stressors, including DNA damage, oncogene activation and physiologic aging, and pathologically accelerated senescence contributes to human disease, including diabetes mellitus. Indeed, recent work in this field has demonstrated a role for pancreatic β-cell senescence in the pathogenesis of Type 1 Diabetes, Type 2 Diabetes and monogenic diabetes. Small molecule or genetic targeting of senescent β-cells has shown promise as a novel therapeutic approach for p… Show more

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Cited by 8 publications
(2 citation statements)
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“…Stressful conditions associated with diabetes reduce Ca 2+ ER stores; this elevates ER stress and initiates the unfolded protein response (UPR), which initially protects β-cells from diabetogenic stress but also limits insulin production and secretion [ 4 , 5 ]. The prolonged disruption of Ca 2+ ER can eventually lead to β-cell failure and/or senescence [ 6 ]. Importantly, alterations in the levels and/or function of the proteins involved in controlling Ca 2+ ER homeostasis can lead to diabetic phenotypes due to β-cell dysfunction.…”
Section: Introductionmentioning
confidence: 99%
“…Stressful conditions associated with diabetes reduce Ca 2+ ER stores; this elevates ER stress and initiates the unfolded protein response (UPR), which initially protects β-cells from diabetogenic stress but also limits insulin production and secretion [ 4 , 5 ]. The prolonged disruption of Ca 2+ ER can eventually lead to β-cell failure and/or senescence [ 6 ]. Importantly, alterations in the levels and/or function of the proteins involved in controlling Ca 2+ ER homeostasis can lead to diabetic phenotypes due to β-cell dysfunction.…”
Section: Introductionmentioning
confidence: 99%
“…Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia [ 1 ]. In Type 1 diabetes (T1D), hyperglycemia is a result of autoimmune destruction of pancreatic beta cells leading to an absolute deficiency of insulin secretion [ 2 ].…”
Section: Introductionmentioning
confidence: 99%