在β细胞模型中,OATP2B1对他类药物的积累和毒性的差异性影响
Jihoon Kwon1, Michelle S Kim1, Christina Blagojevic1
1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Toxicology mechanisms and methods
|September 29, 2023
概括
有机离子运输多2B1 (OATP2B1) 增强了β细胞中的他类药物的积累,增加了毒性. 然而,OATP2B1不会影响他类药物诱导的葡萄糖刺激胰岛素分泌量的减少.
科学领域:
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 类固醇药物治疗与糖尿病风险增加有关,可能对β细胞功能产生影响.
- 有机离子运输多2B1 (OATP2B1) 介导了几个他的肝脏吸收.
- 人类胰腺β细胞表达OATP2B1,这表明OATP2B1在局部他类药物处理中的作用.
研究的目的:
- 调查OATP2B1是否促进大鼠β细胞 (INS-1) 中的他类药物的积累.
- 为了确定OATP2B1是否会放大他类药物诱导的毒性并影响胰岛素分泌.
- 探索OATP2B1对他类药物诱导的线粒体功能障碍和亡的影响.
主要方法:
- 在使用腺病毒载体的INS-1细胞中过度表达OATP2B1.
- 测量罗苏瓦斯塔丁,阿托瓦斯塔丁和普拉瓦斯塔丁的细胞他类药物保留.
- 对亡 (caspase 3/7),线粒体功能 (NADH脱酶) 和胰岛素分泌 (GSIS) 的评估.
主要成果:
- 过度表达OATP2B1显著增加了细胞中罗斯瓦斯塔丁,阿托瓦斯塔丁和普拉瓦斯塔丁的保留.
- 通过使用罗斯瓦斯塔丁和阿托瓦斯塔丁,OATP2B1增强了他类药物诱导的亡和线粒体功能障碍.
- OATP2B1没有影响他类药物诱导的葡萄糖刺激胰岛素分泌或ATP水平的降低.
结论:
- OATP2B1在贝塔细胞内局部积累他类药物的过程中起作用.
- OATP2B1有助于他类药物诱导的毒性,包括细胞亡和线粒体功能障碍.
- 在这个模型中,OATP2B1似乎没有调解他类药物诱导的葡萄糖刺激胰岛素分泌的损害.
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