药学学报, 2021, 56(9): 2447-2455
引用本文:
陈婧文, 柳星峰, 崔冰, 李平平*. 胰高血糖素受体相关化合物研究进展[J]. 药学学报, 2021, 56(9): 2447-2455.
CHEN Jing-wen, LIU Xing-feng, CUI Bing, LI Ping-ping*. Research progress of glucagon receptor related compounds[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2447-2455.

胰高血糖素受体相关化合物研究进展
陈婧文, 柳星峰, 崔冰, 李平平*
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:
2型糖尿病是一种复杂的代谢性疾病,伴有胰岛素抵抗和血糖升高。随着疾病发展,会出现高胰高血糖素血症(hyperglucagonemia)。胰高血糖素(glucagon)促进能量代谢和葡萄糖产生。近年来,胰高血糖素受体(glucagon receptor,GCGR)拮抗类药物被开发,但许多临床研究发现,当拮抗GCGR时,血糖浓度会降低,同时伴有血脂和肝转氨酶增加等不良反应。为解决上述问题,人们发明了胰高血糖素样肽-1受体(glucagon like peptide 1 receptor,GLP-1R)/GCGR共激动剂,其不仅可降低血糖,而且可减轻体重并促进脂肪分解。本文将重点综述GCGR的生物学效应以及GCGR拮抗类药物和GLP-1R/GCGR共激动剂类药物的治疗作用。
关键词:    胰高血糖素受体      糖代谢      胰高血糖素受体拮抗剂      糖尿病      胰高血糖素     
Research progress of glucagon receptor related compounds
CHEN Jing-wen, LIU Xing-feng, CUI Bing, LI Ping-ping*
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Type 2 diabetes is a complex metabolic disease, accompanied by insulin resistance and elevated blood glucose. As the disease progresses, hyperglucagonemia will occur. Glucagon has a significant effect on glucose increase and energy expenditure. In recent years, several glucagon receptor (GCGR) antagonists were developed. They lowered blood glucose in clinical studies, along with side effects, such as increased blood lipids and elevated liver transaminase. In order to solve these problems, glucagon like peptide 1 receptor (GLP-1R)/GCGR co-agonists were developed, which not only lower blood glucose, but also reduce weight and promote lipolysis. In this review, we will focus on the biological effects of glucagon, the treatments of GCGR antagonists, and GLP-1R/GCGR co-agonists on type 2 diabetes.
Key words:    glucagon receptor    glucose metabolism    glucagon receptor antagonist    diabetes    glucagon   
收稿日期: 2021-03-22
DOI: 10.16438/j.0513-4870.2021-0403
基金项目: 国家自然科学基金资助项目(81622010,81770800);中国医学科学院医学与健康科技创新工程(2016-I2M-4-001);中国医学科学院中央级公益性科研院所基本科研业务费(2017PT31046).
通讯作者: 李平平,Tel/Fax:86-10-83161187,E-mail:lipp@imm.ac.cn
Email: lipp@imm.ac.cn
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