Circadian control of β-cell function and stress responses

Diabetes, Obesity & Metabolism
J LeeVijay K Yechoor

Abstract

Circadian disruption is the bane of modern existence and its deleterious effects on health; in particular, diabetes and metabolic syndrome have been well recognized in shift workers. Recent human studies strongly implicate a 'dose-dependent' relationship between circadian disruption and diabetes. Genetic and environmental disruption of the circadian clock in rodents leads to diabetes secondary to β-cell failure. Deletion of Bmal1, a non-redundant core clock gene, leads to defects in β-cell stimulus-secretion coupling, decreased glucose-stimulated ATP production, uncoupling of OXPHOS and impaired glucose-stimulated insulin secretion. Both genetic and environmental circadian disruptions are sufficient to induce oxidative stress and this is mediated by a disruption of the direct transcriptional control of the core molecular clock and Bmal1 on Nrf2, the master antioxidant transcription factor in the β-cell. In addition, circadian disruption also leads to a dysregulation of the unfolded protein response and leads to endoplasmic reticulum stress in β-cells. Both the oxidative and endoplasmic reticulum (ER) stress contribute to an impairment of mitochondrial function and β-cell failure. Understanding the basis of the circadian control...Continue Reading

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Dec 23, 2017·Nature Cell Biology·Miguel Sanchez-Alvarez, Chris Bakal
Dec 29, 2017·Aging·Gongsheng YuanRuizhe Qian
Dec 17, 2016·Diabetologia·Andrew C ForrestelMichael T Sellix
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Apr 3, 2020·General and Comparative Endocrinology·Jessica Paloma Álvarez-Rendón, Juan Rafael Riesgo-Escovar

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