胰高血糖素样肽-1(GLP-1)是一种多功能肠促胰岛素激素,具有多种生理作用,超出了其在胰腺中刺激葡萄糖依赖性胰岛素分泌的特征。GLP-1及其受体的新作用,GLP-1R,在脑神经保护和抑制炎症方面,近年来已被记录在案。GLP-1R是一种G蛋白偶联受体(GPCR),可与刺激第二信使环状3'产生的Gs蛋白偶联。5'-一磷酸腺苷(cAMP)。cAMP,通过它的两个主要效应器起作用,蛋白激酶A(PKA)和cAMP(Epac)直接激活的交换蛋白,在细胞中发挥几种抗炎(和一些促炎)作用,取决于细胞类型。本综述讨论了GLP-1R在心肌细胞中引起的cAMP依赖性分子信号通路,心脏成纤维细胞,中枢神经元,甚至在肾上腺嗜铬细胞中,特别关注通过GLP-1R产生抗炎作用的那些。充分阐明cAMP在GLP-1R的抗炎特性中的作用可以为药物开发带来新的和更精确的靶标,和/或为目前市场上的GLP-1R激动剂药物与其他类别的药物的新型治疗组合提供基础。
Glucagon-like peptide-1 (GLP-1) is a multifunctional incretin hormone with various physiological effects beyond its well-characterized effect of stimulating glucose-dependent insulin secretion in the pancreas. An emerging role for GLP-1 and its receptor, GLP-1R, in brain neuroprotection and in the suppression of inflammation, has been documented in recent years. GLP-1R is a G protein-coupled receptor (GPCR) that couples to Gs proteins that stimulate the production of the second messenger cyclic 3\',5\'-adenosine monophosphate (cAMP). cAMP, acting through its two main effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), exerts several anti-inflammatory (and some pro-inflammatory) effects in cells, depending on the cell type. The present review discusses the cAMP-dependent molecular signaling pathways elicited by the GLP-1R in cardiomyocytes, cardiac fibroblasts, central neurons, and even in adrenal chromaffin cells, with a particular focus on those that lead to anti-inflammatory effects by the GLP-1R. Fully elucidating the role cAMP plays in GLP-1R\'s anti-inflammatory properties can lead to new and more precise targets for drug development and/or provide the foundation for novel therapeutic combinations of the GLP-1R agonist medications currently on the market with other classes of drugs for additive anti-inflammatory effect.