胰升糖素样肽1对胰岛β细胞作用的研究进展

Recent progress in the research of the impact of glucagon-like peptide-1 on islet β-cells

胰升糖素样肽1（GLP-1）是由小肠内L细胞分泌的肠道促胰岛激素，GLP-1与其特异性受体GLP-1受体（GLP-1R）结合后可激活腺苷酸环化酶，生成cAMP，并激活蛋白激酶A及鸟嘌呤核苷酸交换因子（GEF）信号途径，另外GLP-1还可通过不同的方式激活钙调蛋白通路及丝裂原活化蛋白激酶和磷脂酰肌醇3激酶通路，产生多种生理效应。GLP-1可促进胰岛素的1相和2相分泌，增加胰岛素的合成，此外GLP-1还可促进胰岛β细胞的增殖及分化，减少β细胞凋亡，减轻内质网应激对β细胞的损伤作用，增加β细胞存活。

Glucagon-like peptide-1 （ GLP-1 ） is an incretin secreted by the enteroendocrine L cells of the gut. Upon the activation of GLP-1 receptor, adenylyl cyclase is activated and cAMP is generated, leading to the activation of protein kinase A and Epac signal pathway. GLP-1 could also activate calcium/calmodulin pathway as well as mitogen-activated protein kinases and phosphatidyl inositol-3 kinase pathway. GLP-1 not only stimulates the phase 1 and phase 2 insulin secretion, but also increases insulin synthesis. GLP-1 also stimulates proliferation and differentiation of islet β-cells, and protects β-cell from apoptosis and modulates endoplasmic reticulum stress response leading to promotion of β-cell adaptation and survival.