胰岛素抵抗是2型糖尿病的发病基础🤵🏿♂️，也是多种代谢相关性疾病如肥胖、非酒精性脂肪肝病等的共同病理基础，更是心血管疾病的危险因素之一。但目前肝脏胰岛素抵抗的发生机制尚未完全阐明🤷🏿♂️🫲🏿，深入研究肝脏胰岛素抵抗的分子机制对于胰岛素抵抗相关疾病的防治具有十分重要的意义。
2023年12月21日，杏鑫孟丹教授团队在《自然通讯》（Nature Communications🚇，IF 16.6）杂志在线发表了题为《BACH1在小鼠中调控肝脏胰岛素信号通路和葡萄糖稳态》（BACH1 Controls Hepatic Insulin Signaling and Glucose Homeostasis in Mice）的最新研究成果。这项工作表明靶向抑制肝脏BACH1能够明显改善高脂饮食喂养小鼠和db/db糖尿病小鼠的肝脏胰岛素敏感性，改善葡萄糖耐量和糖代谢的异常以及肝脂肪变性🧙🏿♀️。研究阐明了BACH1作为胰岛素信号通路的负调控因子，在调控肝脏胰岛素敏感性和葡萄糖代谢中的重要作用，为胰岛素抵抗相关疾病的防治提供了新的靶点。
https://doi.org/10.1038/s41467-023-44088-z
参考文献
【1】Igarashi, K., Hoshino, H., Muto, A., Suwabe, N., Nishikawa, S., Nakauchi, H. and Yamamoto, M. (1998). Multivalent DNA binding complex generated by small Maf and Bach1 as a possible biochemical basis for beta-globin locus control region complex. J. Biol. Chem. 273, 11783-11790.
【2】Haldar, M., Kohyama, M., So, A.Y., Kc, W., Wu, X., Briseno, C.G., Satpathy, A.T., Kretzer, N.M., Arase, H. and Rajasekaran, N.S., et al. (2014). Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell 156, 1223-1234.
【3】Matsumoto, M., Kondo, K., Shiraki, T., Brydun, A., Funayama, R., Nakayama, K., Yaegashi, N., Katagiri, H. and Igarashi, K. (2016). Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts showed BACH1-Pparg pathway in adipogenesis. Genes Cells 21, 553-567.
【4】Wei, X., Guo, J., Li, Q., Jia, Q., Jing, Q., Li, Y., Zhou, B., Chen, J., Gao, S. and Zhang, X., et al. (2019). Bach1 regulates self-renewal and impedes mesendodermal differentiation of human embryonic stem cells. Sci. Adv. 5, eaau7887.
【5】Jia M, Li Q, Guo J, Shi W, Zhu L, Huang Y, Li Y, Wang L, Ma S, Zhuang T, Wang X, Pan Q, Wei X, Qin Y, Li X, Jin J, Zhi X, Tang J, Jing Q, Li S, Jiang L, Qu L, Osto E, Zhang J, Wang X, Yu B, Meng D. Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation. Circ Res. 2022 Apr;130(7):1038-1055.
【6】Guo J, Qiu J, Jia M, Li Q, Wei X, Li L, Pan Q, Jin J, Ge F, Ma S, He Y, Lin J, Li Y, Ma J, Jiang N, Zhi X, Jiang L, Zhang J, Osto E, Jing Q, Wang X, Meng D. BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility. Nucleic Acids Res. 2023 May 22;51(9):4284-4301.