Annals of medicine · 2025
Clock genes in pancreatic disease progression: from circadian regulation to dysfunction.
СтатьяОбзорПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zheng Tiankuo, Wang Kunpeng, Shi Qiao, Zhang Lilong, Yan Qihao, Jiang Wanrong, Chen Chen, Zhao Kailiang, Feng Jiarui, Wang Weixing
Аннотация
BACKGROUND: Circadian rhythms, governed by core clock genes, are essential for maintaining metabolic, endocrine, and immune homeostasis. Disruption of these rhythms has been increasingly implicated in the pathogenesis of various pancreatic diseases.
OBJECTIVE: This review summarizes current evidence on the role of circadian rhythm disruption in pancreatic diseases, including type 2 diabetes (T2D), type 1 diabetes (T1D), pancreatitis, and pancreatic cancer (PC), with a focus on underlying mechanisms involving clock gene dysregulation.
RECENT FINDINGS: In T2D, dampened oscillations of clock gene expression in pancreatic islets are associated with impaired insulin secretion and loss of cellular synchrony. In T1D, circadian dysregulation enhances immune activation and reduces β-cell tolerance, accelerating disease progression. In pancreatitis, especially in chronic forms, loss of core clock components such as Bmal1 exacerbates pancreatic stellate cell activation, fibrosis, and inflammatory cytokine release. Additionally, circadian disruption has been linked to pancreatic tumorigenesis, suggesting a potential role of clock genes in early cancer development through modulation of the inflammatory microenvironment and stromal remodeling.
CONCLUSION: Circadian clock genes play a multifaceted role in pancreatic disease pathophysiology, extending beyond metabolic regulation to influence immune responses, inflammation, and tumorigenesis. Understanding these mechanisms may inform the development of novel circadian-based therapeutic strategies for pancreatic disorders.
OBJECTIVE: This review summarizes current evidence on the role of circadian rhythm disruption in pancreatic diseases, including type 2 diabetes (T2D), type 1 diabetes (T1D), pancreatitis, and pancreatic cancer (PC), with a focus on underlying mechanisms involving clock gene dysregulation.
RECENT FINDINGS: In T2D, dampened oscillations of clock gene expression in pancreatic islets are associated with impaired insulin secretion and loss of cellular synchrony. In T1D, circadian dysregulation enhances immune activation and reduces β-cell tolerance, accelerating disease progression. In pancreatitis, especially in chronic forms, loss of core clock components such as Bmal1 exacerbates pancreatic stellate cell activation, fibrosis, and inflammatory cytokine release. Additionally, circadian disruption has been linked to pancreatic tumorigenesis, suggesting a potential role of clock genes in early cancer development through modulation of the inflammatory microenvironment and stromal remodeling.
CONCLUSION: Circadian clock genes play a multifaceted role in pancreatic disease pathophysiology, extending beyond metabolic regulation to influence immune responses, inflammation, and tumorigenesis. Understanding these mechanisms may inform the development of novel circadian-based therapeutic strategies for pancreatic disorders.