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伊梅格林林对小鼠周围生理时钟的急性和慢性影响

Yifan Shi¹, Pingping Xu¹, Jun-Ichi Morishige¹

¹Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Journal of pharmacological sciences

|December 13, 2025

概括

伊梅格林 (Imeglimin) 是一种新的糖尿病药物,它会影响小鼠肌肉和肝脏中昼夜钟基因表达. 单剂量和长期使用都改变了基因节律,影响因时间和组织而异.

科学领域:

时间生物学时间生物学
药理学药理学是指药理学的学科.
代谢疾病代谢疾病

背景情况:

循环节律调节生理过程,包括新陈代谢.
昼夜时钟的干扰与糖尿病等代谢障碍有关.
伊梅格林是治疗2型糖尿病的新型治疗剂.

研究的目的:

为了研究伊梅格林对外周生态时钟的影响.
为了检查imeglimin的急性和慢性影响.
评估imeglimin对小鼠时钟基因表达的影响.

主要方法:

使用的是雌性C57BL/6J小鼠.
急性研究:单次口服伊梅格林胺剂量在Zeitgeber时间 (ZT) 0或ZT 12.
慢性研究:在中含有0.2%的美格林,持续4周.
时钟基因mRNA表达通过骨肌肉和肝脏的定量实时PCR分析.

主要成果:

在ZT 12的急性伊梅格林增加了肌 (Nr1d1,Dbp) 和肝脏 (Per2) 中的峰值时钟基因mRNA表达.
在ZT0时的急性伊梅格林在两个组织中减少了Nr1d1和DbpmRNA表达.
慢性伊梅格林在骨肌肉中降低了Nr1d1峰值和Dbp表达;肝脏节律没有受到影响.
在两个组织中,Nampt和Sirt1的表达保持不变.

结论:

伊梅格林胺改变了小鼠的外周时钟基因表达.
在急性和慢性服用条件下都观察到影响.
需要进一步的研究来了解机制和生理学意义.

关键词:

循环节的时钟是循环节的时间.时钟基因是指时间基因.我已经消除了这个问题.骨架肌肉是一个骨肌肉.

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