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C2C12 细胞模型:在分子水平理解胰岛素抵抗和临床前阶段药物开发中的作用。

C2C12 cell model: its role in understanding of insulin resistance at the molecular level and pharmaceutical development at the preclinical stage.

机构信息

School of Pharmacy and Biomedical Science, Curtin University, Bentley, WA, Australia.

Curtin Health Innovation Research Institute, Bentley, WA, Australia.

出版信息

J Pharm Pharmacol. 2020 Dec;72(12):1667-1693. doi: 10.1111/jphp.13359. Epub 2020 Aug 18.

Abstract

OBJECTIVES

The myoblast cell line, C2C12, has been utilised extensively in vitro as an examination model in understanding metabolic disease progression. Although it is indispensable in both preclinical and pharmaceutical research, a comprehensive review of its use in the investigation of insulin resistance progression and pharmaceutical development is not available.

KEY FINDINGS

C2C12 is a well-documented model, which can facilitate our understanding in glucose metabolism, insulin signalling mechanism, insulin resistance, oxidative stress, reactive oxygen species and glucose transporters at cellular and molecular levels. With the aid of the C2C12 model, recent studies revealed that insulin resistance has close relationship with various metabolic diseases in terms of disease progression, pathogenesis and therapeutic management. A holistic, safe and effective disease management is highly of interest. Therefore, significant efforts have been paid to explore novel drug compounds and natural herbs that can elicit therapeutic effects in the targeted sites at both cellular (e.g. mitochondria, glucose transporter) and molecular level (e.g. genes, signalling pathway).

SUMMARY

The use of C2C12 myoblast cell line is meaningful in pharmaceutical and biomedical research due to their expression of GLUT-4 and other features that are representative to human skeletal muscle cells. With the use of the C2C12 cell model, the impact of drug delivery systems (nanoparticles and quantum dots) on skeletal muscle, as well as the relationship between exercise, pancreatic β-cells and endothelial cells, was discovered.

摘要

目的

成肌细胞系 C2C12 在体外作为代谢疾病进展研究的检查模型被广泛应用。尽管它在临床前和药物研究中都是不可或缺的,但目前尚无关于其在胰岛素抵抗进展和药物开发研究中的综合应用的综述。

主要发现

C2C12 是一个有充分文献记载的模型,可促进我们在细胞和分子水平上对葡萄糖代谢、胰岛素信号机制、胰岛素抵抗、氧化应激、活性氧和葡萄糖转运蛋白的理解。借助 C2C12 模型,最近的研究表明,胰岛素抵抗与各种代谢疾病在疾病进展、发病机制和治疗管理方面密切相关。因此,人们非常关注整体、安全和有效的疾病管理。因此,人们付出了巨大的努力来探索新型药物化合物和天然草药,这些化合物和草药可以在细胞(如线粒体、葡萄糖转运蛋白)和分子水平(如基因、信号通路)的靶向部位发挥治疗作用。

总结

由于 C2C12 成肌细胞系表达 GLUT-4 及其它与人类骨骼肌细胞具有代表性的特征,因此在药物和生物医学研究中使用 C2C12 成肌细胞系具有重要意义。通过使用 C2C12 细胞模型,发现了药物输送系统(纳米粒子和量子点)对骨骼肌的影响,以及运动、胰腺β细胞和内皮细胞之间的关系。

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