Novel nonapeptide GLP (28-36) amide derivatives with improved hypoglycemic and body weight lowering effects
Novel nonapeptide GLP (28-36) amide derivatives with improved hypoglycemic and body weight lowering effects
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具有改善降血糖和减轻体重作用的新型九肽 GLP (28-36) 酰胺衍生物
DOI：
10.1016/j.bmc.2019.03.014
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发表时间：
2019
影响因子：
3.5
通讯作者：
Sun Lidan
中科院分区：
文献类型：
--
作者：
Li Leyao;Wu Lingling;Xia E;Yan Wenru;Cai Xingguang;Han Jing;Sun Lidan
胰高血糖素样肽-1（GLP-1）已成为治疗2型糖尿病的主要治疗靶点。九肽GLP-1（28-36）酰胺是GLP-1的生物C-末端产物之一，由中性内肽酶（NEP）24.11修饰，具有有限的降血糖活性。本研究首次对GLP-1（28-36）酰胺进行了修饰，合成了一系列GLP-1（28-36）酰胺类似物。在INS-1细胞、STZ诱导的糖尿病和饮食诱导的肥胖（DIO）小鼠中的生物活性评价结果表明，S3是治疗2型糖尿病和肥胖的有希望的候选物。
Glucagon-like peptide-1 (GLP-1) has emerged as a major therapeutic target for the treatment of type 2 diabetes. The nonapeptide GLP-1 (28–36) amide is one of the biological C-terminal products of GLP-1 modified by the neutral endopeptidase (NEP) 24.11 with limited hypoglycemic activity. In this study, we focused on the modification of GLP-1 (28–36) amide for the first time and synthesized a series of GLP-1 (28–36) amide analogues. Results of biological activity evaluation in INS-1 cell, STZ-induced diabetic and diet induced obesity (DIO) mice indicated that S3 as a promising candidate to treat type 2 diabetes and obesity.