胰岛素对代谢的中枢调控作用  

Central Action of Insulin on Metabolism

作　　者：张健维 王俊博 王梦远 刘佳瑞 刘讷鸥 郑瑞茂[1] ZHANG Jian-Wei;WANG Jun-Bo;WANG Meng-Yuan;LIU Jia-Rui;LIU Ne-Ou;ZHENG Rui-Mao(Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University; Neuroscience Research Institute, Peking University; Key Laboratory for Neuroscience of Ministry of Education; Key Laboratory for Neuroscience of National Health Commission, Beijing 100191, China)

机构地区：[1]北京大学基础医学院人体解剖与组织胚胎学系北京大学神经科学研究所教育部神经科学重点实验室国家卫生健康委员会神经科学重点实验室,北京100191

出　　处：《生理科学进展》2018年第6期401-410,共10页Progress in Physiological Sciences

基　　金：国家自然科学基金(81471064; 81670779; 81870590);北京市自然科学基金(7162097);国家重点研发计划项目(2017YFC1700402);北京大学优秀青年人才引进计划科研启动基金(BMU20140366);北京大学基础医学院创新人才培养项目资助课题;京津冀基础研究合作项目基金(H2018206641)

摘　　要：胰岛素(insulin)为机体重要降糖激素,可促进葡萄糖氧化利用、促进脂肪蛋白质及肝糖原肌糖原合成;并抑制胰高血糖素分泌及肝糖原与脂肪分解;在血糖平衡与代谢稳态调控中发挥关键作用。经典理论认为,胰岛素由胰腺β细胞分泌,经体液途径,与靶细胞胰岛素受体(insulin receptor)结合以启动细胞信号传导而发挥作用。然而,在过去三十年间,胰岛素作用于中枢神经系统,经神经机制调控机体糖代谢稳态的作用,亦陆续被报道。近年来,随着神经科学与代谢学新技术发展,胰岛素对代谢稳态的中枢调控机制,得以被深入研究;与此相关的脑区、神经核团、神经元、细胞信号传导通路、神经通路陆续被揭示。值得关注的是,脑内胰岛素作用异常,亦是引发代谢相关疾病,如肥胖、2型糖尿病等疾病的重要因素之一。目前,以中枢为靶点的降糖药相继问世,可有效降低血糖、减轻胰岛素抵抗、改善2型糖尿病症状。由于肥胖、2型糖尿病等代谢疾病呈全球高发趋势,探索胰岛素对代谢的中枢调控机制,具重大医学与社会意义;因此,本文综述五年来相关研究进展,以期深入认识胰岛素生理作用,并为相关疾病机理与诊疗提供新思路。Insulin is a hypoglycemic hormone.Insulin also stimulates glucose utilization;promotes protein synthesis,hepatic and muscle glycogenesis;inhibits glucagon secretion,glycogenolysis and lipolysis.Insulin plays an important role in the regulation of glucose balance and metabolic homeostasis.According to classical theory,insulin is produced byβcells of pancreatic islets,and binds to its receptor on target cells to initiate the insulin signal transduction to exert its function through a humoral pathway.However,over the past thirty years,accumulative evidence demonstrates that insulin also targets central nervous system(CNS)to regulate metabolic homeostasis.In recent years,with the development of novel technology in neuroscience and metabolism,the central action of insulin on the metabolic homeostasis has been intensively investigated,which revealed a series of brain regions,nervous nuclei,neurons,cellular signalings,and neural pathways linked to insulin central function.Notably,dysfunction of insulin in brain contributes to metabolic disorders including obesity,type-2diabetes mellitus.The anti-diabetic drugs targeted on CNS show promising effects in reducing blood glucose,and relieving insulin resistance.The prevalence of obesity and type2diabetes mellitus is increasing worldwide,we thus summarized the progress made during the last five years for providing new insights into the mechanism by which insulin centrally regulates the metabolism as well as the novel therapeutic strategy for metabolic diseases.

关 键 词：胰岛素 中枢神经系统 胰岛素抵抗 信号通路 神经通路 

分 类 号：R33[医药卫生—人体生理学] R34[医药卫生—基础医学]