游离脂肪酸受体1对胰岛素分泌的调控作用及相关药物开发进展  

The regulation of FFAR1 on insulin secretion and the development of related drugs

作　　者：贾伟华 杨秀颖 杜冠华 JIA Wei-hua, YANG Xiu-ying, DU Guan-hua(State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Matria Medica, Chinese Accademy of Medical Sciences and Peking Union Medical College, Beijing 100050, China)

机构地区：[1]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药物靶点研究与新药筛选北京市重点实验室,北京100050

出　　处：《药学学报》2018年第11期1770-1777,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金面上项目资助(81470159;81770847);中国医学科学院医学与健康科技创新工程(2016-I2M-3-007;2017-I2M-1-010);国家重点研发计划(2016YFC1000905)

摘　　要：游离脂肪酸受体1(free fatty acid receptor 1,FFAR1),也称G蛋白偶联受体40(G protein-coupled receptor 40,GPR40),是中长链游离脂肪酸的受体。本综述旨在总结该受体在胰岛素分泌及调控糖脂代谢方面的作用及研究进展。FFAR1参与糖尿病的发生发展,但其具体作用机制尚未明确。FFAR1在多种组织中均有表达,主要表达于胰岛β细胞,其他组织有胰岛α细胞、中枢神经系统、皮下脂肪、肌肉、胃肠道等。FFAR1可作用于胰岛β细胞,促进胰岛素分泌,促进胰岛α细胞分泌胰高血糖素;调控胃肠道内分泌细胞调控糖脂水平。现有研究发现,FFAR1激动剂可促进胰岛素释放,降低体重及保护β细胞,而且没有低血糖的风险,具有明显优势。对FFAR1靶点的深入药理机制研究,可评价其作为糖尿病治疗药物靶点的可能性,有利于高效、安全的抗2型糖尿病药物开发。Free fatty acid receptor 1（FFAR1）,also known as G protein-coupled receptor 40（GPR40）,is a receptor for diverse free fatty acids.This review aims at summarizing effects and mechanisms of FFAR1 on insulin secretion and related blood glucose and lipids metabolism.FFAR1 is involved in the occurrence and development of type 2 diabetes,but its specific mechanism has not been clarified.FFAR1 is expressed in the wide variety of issues,especially β-cells in the pancreatic islets,as well as α-cells in islets,central nervous tissue,subcutaneous fat,skeletal muscle,gastrointestinal tract,etc.FFAR1 can act on islet β-cells to promote the secretion of insulin,promote α-cells on glucagon secretion,and regulate the secretion of endocrine cells in the gastrointestinal tract to balance the level of glucose and lipids.Existing research found that FFAR1 agonists have significant advantages.They promote insulin release,reduce weight and protect pancreatic β-cells,and have no risk of hypoglycemia.To in-depth understand the role of FFAR1 as a drug target in the treatment of diabetes,further pharmacological studies are still needed in order to obtain safer and more effective drugs against type 2 diabetes.

关 键 词：游离脂肪酸受体1 2型糖尿病 游离脂肪酸 胰岛素 

分 类 号：R966[医药卫生—药理学]