每1
昼夜节律
生物钟
时钟
生物
内分泌学
细胞生物学
内科学
胚胎干细胞
基因表达
基因
医学
遗传学
作者
Kotomi Miura,Jun‐ichi Morishige,Jotaro Abe,Pingping Xu,Yifan Shi,Zheng Jing,Naoto Nagata,Ryo Miyazaki,Naoki Sakane,Michihiro Mieda,Masanori Ono,Yoshiko Maida,Tomoko Fujiwara,Hiroshi Fujiwara,Hitoshi Ando
标识
DOI:10.1016/j.jphs.2023.10.001
摘要
Imeglimin is a novel antidiabetic drug structurally related to metformin. Metformin has been shown to modulate the circadian clock in rat fibroblasts. Accordingly, in the present study, we aimed to determine whether imeglimin can impact the circadian oscillator in mouse embryonic fibroblasts (MEFs).MEFs carrying a Bmal1-Emerald luciferase (Bmal1-ELuc) reporter were exposed to imeglimin (0.1 or 1 mM), metformin (0.1 or 1 mM), a nicotinamide phosphoribosyltransferase inhibitor FK866, and/or vehicle. Subsequently, Bmal1-ELuc expression and clock gene mRNA expression levels were measured at 10-min intervals for 55 h and 4-h intervals for 32 h, respectively.Imeglimin significantly prolonged the period (from 26.3 to 30.0 h at 0.1 mM) and dose-dependently increased the amplitude (9.6-fold at 1 mM) of the Bmal1-ELuc expression rhythm; however, metformin exhibited minimal effects on these parameters. Moreover, imeglimin notably impacted the rhythmic mRNA expression of clock genes (Bmal1, Per1, and Cry1). The concurrent addition of FK866 partly inhibited the effects of imeglimin on both Bmal1-ELuc expression and clock gene mRNA expression.Collectively, these results reveal that imeglimin profoundly affects the circadian clock in MEFs. Further studies are needed to evaluate whether imeglimin treatment could exert similar effects in vivo.
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