天津医药

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胰高血糖素样肽1及其受体激动剂研究进展

付刚,龚珉,徐为人   

  1. 天津药物研究院
  • 收稿日期:2011-01-26 修回日期:2011-05-18 出版日期:2012-02-15 发布日期:2012-02-15
  • 通讯作者: 龚珉

Development of Glucagon-like Peptide-1 Analogs and GLP-1 Receptor Agonists

  • Received:2011-01-26 Revised:2011-05-18 Published:2012-02-15 Online:2012-02-15

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摘要： 胰高血糖素样肽1 (Glucagon-like Peptide-1，GLP-1) 是一种由肠道Ｌ细胞分泌的多肽激素，其与GLP-1受体结合后具有促进胰岛素分泌和生物合成，抑制胰高血糖素的分泌，促进胰岛?细胞增殖，抑制胰岛?细胞凋亡，保存?细胞对血糖的敏感性等多种生理功能，但是其在体内的半衰期很短 (<2 min)，在临床应用上很受限制。根据GLP-1及其受体设计GLP-1类似物是目前开发糖尿病新药的前沿靶点之一，旨在寻找能够耐受二肽基肽酶4(DPP4)降解并具有GLP-1生理活性的长效肽类及非肽类化合物。本文对GLP-1及其受体激动剂的研究成果综述如下。

关键词: 2型糖尿病, 胰高血糖素样肽1, GLP-1受体, 肠促胰岛素, 长效GLP1R激动剂

Abstract: Glucagon-like peptide-1(GLP-1) is a hormone secreted from enteroendocrine L cells of the intestine. Upon binding to its receptor, it results in many effects such as increasing insulin biosynthesis and secretion from β cells; suppressing glucagon secretion from α cells; enhancing islet neogenesis and proliferation of β cells; decreasing apoptosis of β cells; enhancing body sensibility to insulin and so on. However, GLP-1 is rapidly degraded by DPP IV enzyme and clearance in renal; the in vivo half-life is less than 2 min which limited the clinical utility of GLP-1 in type 2 diabetes. Many efforts were focused on finding the novel GLP-1 receptor agonist or GLP-1 analogs retaining the biological effects of GLP-1. This review summarized the physiological properties of GLP-1 and the ongoing development of GLP-1-based therapies for treatment of diabetes.

Key words: Type 2 diabetes, Glucagon-like peptide-1, GLP-1 receptor, Incretin, long-acting GLP-1R agonist