药学学报, 2017, 52(5): 667-672
引用本文:
王悦, 刘率男, 申竹芳. 线粒体-内质网动态关联与胰岛β细胞功能稳态[J]. 药学学报, 2017, 52(5): 667-672.
WANG Yue, LIU Shuai-nan, SHEN Zhu-fang. Dynamic associations of mitochondria-endoplasmic reticulum in maintenance of pancreatic beta cell homeostasis[J]. Acta Pharmaceutica Sinica, 2017, 52(5): 667-672.

线粒体-内质网动态关联与胰岛β细胞功能稳态
王悦, 刘率男, 申竹芳
中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050
摘要:
胰岛β细胞内的能量及物质代谢稳态是维持其正常功能及存活的关键,细胞器线粒体与内质网之间的动态关联在此过程中起到了重要的调控作用。线粒体自身的动态变化响应胞内能量和物质代谢,为胰岛β细胞稳态提供物质基础;内质网则可根据线粒体的变化,实时调节相关代谢酶及蛋白的合成,从而调控胰岛β细胞功能。本文将综述近年围绕线粒体与内质网间动态联系的相关研究,阐述二者通过结构或功能变化,相互影响、协同作用,进而维持胰岛β细胞正常状态以及生理功能的过程。线粒体与内质网之间的动态关联,以全新视角对胰岛β细胞损伤及保护的可能途径进行了阐释,其中也不乏一些潜在的药物治疗靶点,对于2型糖尿病的相关机制探讨及新药研发具有十分重要的意义。
关键词:    线粒体      内质网      胰岛β细胞      物质代谢      2型糖尿病     
Dynamic associations of mitochondria-endoplasmic reticulum in maintenance of pancreatic beta cell homeostasis
WANG Yue, LIU Shuai-nan, SHEN Zhu-fang
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
The appropriate regulation of intracellular bioenergy and nutrient metabolism is a basic requirement for proper function and survival of pancreatic beta cells, where mitochondria-endoplasmic reticulum (ER)-associations play crucial roles. Mitochondria are changed dynamically according to intracellular energy and nutrients, which provides material foundation for energy homeostasis; while ER regulates metabolic enzymes and protein synthesis in different pathways. This review sheds light upon the development of mitochondria-ER associations and its role in the regulation of insulin secretion in pancreatic beta cell. The impact on beta cell viability is discussed. Interruption of calcium and redox oxidative species results in reduction of glucose-stimulated insulin secretion, while intracellular calcium levels could be partial altered by depleting calcium from the ER. Given the tight link between ER and mitochondria, the association are crucial to the homeostasis and are an indicator of overall beta cell status, with a potential as a novel drug target for treatment of type 2 diabetes mellitus.
Key words:    mitochondria    endoplasmic reticulum    pancreatic beta cell    nutrient metabolism    type 2 diabetes mellitus   
收稿日期: 2016-11-24
DOI: 10.16438/j.0513-4870.2016-1132
基金项目: 国家自然科学基金资助项目(81202574);北京市自然科学基金资助项目(7132162);重大新药创制国家科技重大专项资助项目(2012ZX09301002-004).
通讯作者: 申竹芳,Tel:86-10-83172669,E-mail:shenzhf@imm.ac.cn
Email: shenzhf@imm.ac.cn
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