胰高血糖素样肽-1在胰腺中作用机制的研究进展

胰高血糖素样肽-1（GLP-1）是胰高血糖素原基因编码的一种激素,主要由肠道L细胞产生并分泌进入血液。GLP-1能激活胰腺、肾脏、肺、胃、心脏和脑等组织中存在的特异性G蛋白偶联受体（GPCR）。通过GLP-1受体（GLP-1R）的激活,活化腺苷酸环化酶,产生3＇,5＇-环腺苷酸,随后通过cAMP依赖性第二信使途径激活蛋白激酶A和鸟苷酸交换因子。大量围绕胰岛素产生细胞——β细胞开展的研究证明,GLP-1短期作用能够加强葡萄糖依赖性的胰岛素分泌作用,持续的GLP-1R激活也能增加胰岛素的合成,促进β细胞的增殖和新生,抑制β细胞凋亡。GLP-1在胰岛素和胰高血糖素分泌方面的独特作用引发了大量针对GLP-1受体激动剂的研究。我们对胰腺中GLP-1R激活所产生作用的机制进行简要综述。

Mechanisms of Effects of Glucagon-Like Peptide 1 in the Pancreas

Hormone glucagon-like peptide I（GLP-1） is a product from proglucagon gene. It is mainly produced in L cells of the gut and is secreted into the blood stream. GLP-1 engages a specific guanine nucleotide-binding protein （Gprotein） coupled receptor that presents in tissues such as pancreas, brain, kidney, lung, stomach and heart. Upon GLP-1 receptor（GLP-1R） activation, adenylyl cyclase is activated and cAMP is generated, leading to cAMP dependent activation of second messenger pathways, such as the protein kinase A and cAMP-regulated guanine nucleotide exchange factor（known as Epac） pathways. The most widely studied cell activated by GLP-1 is the insulin-secreting β cell where its short-term effect is enhancing glucose-induced insulin secretion, continuous GLP-1R activation also increases insulin synthesis, βcell proliferation and neogenesis, inhibits apoptosis. Its particular effects on insulin and glucagon secretion have generated a flurry of research about GLP-1R agonist. This review will focus on mechanisms of the effects resulting from GLP-1R acti- vation in the pancreas.