AbMole丨Liraglutide：GLP-1R激动剂在代谢及纤维化研究中的应用

Liraglutide（利拉鲁肽，AbMole，M45167）是一种长效的人源化GLP-1类似物，通过激活GLP-1受体（GLP-1R），调节cAMP-PKA路径影响代谢，如激活AMPK信号以改善能量代谢和抑制细胞凋亡。在细胞实验中，Liraglutide（CAS No.：204656-20-2）在SH-SY5Y人神经母细胞瘤细胞（10-100nM）中减轻β-淀粉样蛋白引起的毒性并逆转胰岛素抵抗[1]，Liraglutide在MC3T3-E1小鼠成骨细胞（100 nM）中促进成骨分化和增加碱性磷酸酶活性[2]，在HepG2人肝癌细胞（以1-1000 nM的浓度进行实验）抑制细胞增殖和诱导G1/S期停滞[3]。Liraglutide（利拉鲁肽）还能抑制βTC-6小鼠β细胞由血清剥夺诱导的细胞凋亡。Liraglutide还是研究动物代谢的重要工具。Liraglutide能用于C57BL/6J小鼠肥胖模型（1mg/kg剂量）并改善高脂饮食诱导的代谢紊乱以及调节肠道菌群[4]，Liraglutide还在大鼠糖尿病模型（Alloxan 或Streptozotocin（STZ）诱导）减轻了体重和改善血糖控制[5-7]。Liraglutide还能在Sprague Dawley大鼠心肌梗死模型改善心脏功能和减少心肌纤维化[8]。并且Liraglutide在Sprague Dawley大鼠肌肉萎缩模型（200μg/kg/day皮下注射）中成功激活cAMP信号抑制萎缩[9]。Liraglutide还具有一定的抗纤维化活性，在大鼠肺纤维化模型（Bleomycin 诱导）中成功减少了胶原表达[10]。

参考文献及鸣谢

[1] Jantrapirom, S.; Nimlamool, W.; Chattipakorn, N.; et al. Liraglutide Suppresses Tau Hyperphosphorylation, Amyloid Beta Accumulation through Regulating Neuronal Insulin Signaling and BACE-1 Activity. International journal of molecular sciences 2020, 21 (5).

[2] Sun, Y.; Liang, Y.; Li, Z.; et al. Liraglutide Promotes Osteoblastic Differentiation in MC3T3-E1 Cells by ERK5 Pathway. International journal of endocrinology 2020, 2020, 8821077.

[3] Kapodistria, K.; Tsilibary, E. P.; Kotsopoulou, E.; et al. Liraglutide, a human glucagon-like peptide-1 analogue, stimulates AKT-dependent survival signalling and inhibits pancreatic beta-cell apoptosis. Journal of cellular and molecular medicine 2018, 22 (6), 2970-2980.

[4] Zhao, L.; Chen, Y.; Xia, F.; et al. A Glucagon-Like Peptide-1 Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota. Frontiers in endocrinology 2018, 9, 233.

[5] Mathieu, C.; Zinman, B.; Hemmingsson, J. U.; et al. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes care 2016, 39 (10), 1702-1710.

[6] Cai, H.; Zhou, L.; Liu, J.; et al. Independent and combined effects of liraglutide and aerobic interval training on glycemic control and cardiac protection in diabetic cardiomyopathy rats. Biochemical and biophysical research communications 2022, 629, 112-120.

[7] Zhao, X. Y.; Yu, T. T.; Liu, S.; et al. Effect of liraglutide on endoplasmic reticulum stress in the renal tissue of type 2 diabetic rats. World journal of diabetes 2020, 11 (12), 611-621.

[8] Huang, D. D.; Huang, H. F.; Yang, Q.; et al. Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice. European review for medical and pharmacological sciences 2018, 22 (14), 4648-4656.

[9] Gurjar, A. A.; Kushwaha, S.; Chattopadhyay, S.; et al. Long acting GLP-1 analog liraglutide ameliorates skeletal muscle atrophy in rodents. Metabolism: clinical and experimental 2020, 103, 154044.

[10] Yang, X.; Ma, X.; Don, O.; et al. Mesenchymal stem cells combined with liraglutide relieve acute lung injury through apoptotic signaling restrained by PKA/beta-catenin. Stem cell research & therapy 2020, 11 (1), 182.