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Taurine promotes insulin synthesis by enhancing Isl-1 expression through miR-7a/RAF1/ERK1/2 pathway
In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2023-12-20 , DOI: 10.1007/s11626-023-00835-6
Hui Liu , Tongjuan Niu , Guobin Qiu , Sheng Cui , Di Zhang

It has been well established that the circulating taurine affects the insulin synthesis in pancreatic islet β-cells, whereas miR-7a and LIM-homeodomain transcription factor Isl-1 are important intracellular factors regulating insulin transcription and synthesis. However, it still remains unknown whether taurine regulates insulin synthesis by affecting miR‐7a and/or Isl-1 expressions in mouse pancreatic islet β-cells. The present study was thus proposed to identify the effects of taurine on the expressions of miR‐7a and/or Isl-1 and their relations to insulin synthesis in mouse pancreatic islet β-cells by using miR-7a2 knockout (KO) and taurine transporter (TauT) KO mouse models and the related in vitro experiments. The results demonstrated that taurine supplement significantly decreased the pancreas miR-7a expression, but sharply upregulated the pancreas Isl-1 and insulin expressions, and serum insulin levels. However, the enhanced effects of taurine on Isl-1 expression and insulin synthesis were mitigated in the TauT KO and miR-7a2 KO mice. In addition, our results confirmed that taurine markedly increased pancreas RAF1 and ERK1/2 expressions. Collectively, the present study firstly demonstrates that taurine regulates insulin synthesis through TauT/miR-7a/RAF1/ERK1/2/Isl-1 signaling pathway, which are crucial for our understanding the mechanisms of taurine affecting insulin synthesis, and also potential for establishing the therapeutic strategies for diabetes and the diseases related to metabolism.



中文翻译:

牛磺酸通过 miR-7a/RAF1/ERK1/2 通路增强 Isl-1 表达,促进胰岛素合成

众所周知,循环牛磺酸影响胰岛β细胞的胰岛素合成,而miR-7a和LIM同源域转录因子Isl-1是调节胰岛素转录和合成的重要细胞内因子。然而,牛磺酸是否通过影响小鼠胰岛β细胞中的miR-7a和/或Isl-1表达来调节胰岛素合成仍不清楚。因此,本研究旨在通过使用 miR-7a2 敲除(KO)和牛磺酸转运蛋白来确定牛磺酸对小鼠胰岛 β 细胞中 miR-7a 和/或 Isl-1 表达的影响及其与胰岛素合成的关系(TauT) KO小鼠模型及相关体外实验。结果表明,补充牛磺酸显着降低胰腺miR-7a表达,但急剧上调胰腺Isl-1和胰岛素表达以及血清胰岛素水平。然而,牛磺酸对 Isl-1 表达和胰岛素合成的增强作用在 TauT KO 和 miR-7a2 KO 小鼠中减弱。此外,我们的结果证实牛磺酸显着增加胰腺 RAF1 和 ERK1/2 的表达。总的来说,本研究首次证明牛磺酸通过TauT/miR-7a/RAF1/ERK1/2/Isl-1信号通路调节胰岛素合成,这对于我们理解牛磺酸影响胰岛素合成的机制至关重要,也有可能建立糖尿病和代谢相关疾病的治疗策略。

更新日期:2023-12-20
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