Li Shujun, Huang Nanqu, Wang Mei, Huang Wendi, Luo Yong, Huang Juan
Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
National Drug Clinical Trial Institution, Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China.
Front Pharmacol. 2025 May 30;16:1610512. doi: 10.3389/fphar.2025.1610512. eCollection 2025.
Diabetes mellitus (DM), a metabolic disorder syndrome characterized by persistent hyperglycemia, has a complex pathogenesis. As the number of diabetic patients continues to grow globally, this disease has become a major and growing challenge in global public health. Glucagon-like peptide-1 receptor (GLP-1R) is a G protein-coupled receptor widely expressed on the surface of a wide range of cells in the human body, including pancreatic islet α, β and δ cells, as well as multiple tissues such as the intestines, stomach, lungs, heart, kidneys, and central nervous system. GLP-1R works through the combination of the endogenous ligand Glucagon-like peptide-1 (GLP-1) or exogenous agonists, which activate multiple intracellular signaling pathways that enhance insulin secretion, inhibit glucagon secretion, protect β-cells from apoptosis, delay gastric emptying and increase satiety. This makes GLP-1R a key target for diabetes treatment. This paper reviews the structural and functional characteristics of GLP-1R. Its role in glucose homeostasis and its application in diabetes treatment. It focuses on the mechanism of action of GLP-1R in pancreatic islet α-cells, β-cells and δ-cells, as well as its effects on the central nervous system and gastrointestinal tract. In addition, the article reviews the clinical progress of GLP-1R agonists, including their efficacy, safety and potential in the treatment of diabetes and related complications.
糖尿病（DM）是一种以持续性高血糖为特征的代谢紊乱综合征，其发病机制复杂。随着全球糖尿病患者数量持续增长，该疾病已成为全球公共卫生领域一个日益严峻的重大挑战。胰高血糖素样肽-1受体（GLP-1R）是一种G蛋白偶联受体，广泛表达于人体多种细胞表面，包括胰岛α细胞、β细胞和δ细胞，以及肠道、胃、肺、心脏、肾脏和中枢神经系统等多种组织。GLP-1R通过内源性配体胰高血糖素样肽-1（GLP-1）或外源性激动剂的结合发挥作用，激活多种细胞内信号通路，从而增强胰岛素分泌、抑制胰高血糖素分泌、保护β细胞免于凋亡、延缓胃排空并增加饱腹感。这使得GLP-1R成为糖尿病治疗的关键靶点。本文综述了GLP-1R的结构和功能特征、其在葡萄糖稳态中的作用以及在糖尿病治疗中的应用。重点阐述了GLP-1R在胰岛α细胞、β细胞和δ细胞中的作用机制，以及对中枢神经系统和胃肠道的影响。此外，文章还综述了GLP-1R激动剂的临床进展，包括其在糖尿病及相关并发症治疗中的疗效、安全性和潜力。
