近年来糖尿病的发病率日益增加，现已成为继心血管病和肿瘤之后，第3位威胁人们健康和生命的非传染性疾病。GLP-1受体是一种G蛋白偶联受体（GPCR），它可以被GLP-1激活，降低人体的血糖浓度，是用于治疗糖尿病的重要的药物靶标。2018年，GLP-1受体激动剂药物市场规模达到93亿美元，增长率高达25%。两年来，若干GLP-1受体复合物的晶体及电镜结构得到解析，表明GLP-1受体的结构生物学研究瓶颈已经突破。我们将使用液体核磁共振（NMR），结合非天然氨基酸（UAA）标记，分段标记，顺磁弛豫增强（PRE）等手段，研究GLP-1受体与GLP-1激动剂结合的相互作用和构象的动态性质，得出配体对GLP-1受体的构象状态的平衡分布影响的动态信息。此项研究将对理解GLP-1受体的信号传导的分子机制发挥重要作用，为进一步改良糖尿病药物提供理论基础。

The incidence of diabetes has increased in recent years, and it has become the third non-communicable disease that threatens people's health and life after cardiovascular diseases and cancer. The GLP-1 receptor is a G-protein coupled receptor (GPCR) that is activated by GLP-1 and lowers blood glucose levels in humans. It is an important drug target for the treatment of diabetes. In 2018, the GLP-1 receptor agonist drug market reached $9.3 billion, a growth rate of 25%. In the past two years, the crystal and electron microscopic structures of several GLP-1 receptor complexes have been resolved, indicating that the bottleneck of structural biology research of GLP-1 receptors has been broken. We will use liquid nuclear magnetic resonance (NMR), combined with unnatural amino acid (UAA) labeling, segmentation labeling, and paramagnetic relaxation enhancement (PRE) to study the interaction of GLP-1 receptors with GLP-1 agonists. And the dynamic nature of the conformation, resulting in dynamic information on the effect of ligand on the equilibrium distribution of the conformational state of the GLP-1 receptor. This study will play an important role in understanding the molecular mechanisms of GLP-1 receptor signaling and provide a theoretical basis for further improvement of diabetes drugs.