Novel lipid side chain modified exenatide analogs emerged prolonged glucoregulatory activity and potential body weight management properties
Novel lipid side chain modified exenatide analogs emerged prolonged glucoregulatory activity and potential body weight management properties
复制标题
新型脂质侧链修饰的艾塞那肽类似物出现了延长的葡萄糖调节活性和潜在的体重管理特性
DOI：
10.1016/j.bmc.2019.115070
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发表时间：
2019
影响因子：
3.5
通讯作者：
Hai Qian
中科院分区：
文献类型：
--
作者：
Chengye Li;Xingguang Cai;Yuxuan Dai;Chunxia Liu;Xinzhou Bi;Jiaqi Zhou;Qifei Li;Lidan Sun;Wenlong Huang;Zhibo Hou;Hai Qian
Exenatide is known as the first marketed GLP-1 agonist for antidiabetic treatment, but it need twice injection a day because of its fast clearance. This work aims to prolong the half-life of exenatide by modified with novel lipid chain. Four optimized exenatide analogs named as Cys12-Exenatide (1–39)-NH2, Cys40-Exenatide (1–39)-NH2, Cys12-Tyr22-Gln24-Glu28-Arg35-Exenatide (1–39)-NH2and Tyr22-Gln24-Glu28-Arg35-Cys40-Exenatide (1–39)-NH2were selected and applied for conjugation. Then a series of evaluations including GLP-1R activation assay were conducted, conjugationC2was selected for further investigation. Glucoregulatory and insulin secretion assay and hypoglycemic duration test were accessed and showed thatC2was capable of comparable insulinotropic activities and glucose-lowering abilities with those of liraglutide and exenatide. Cell protective effects in INS-1 cells confirmed thatC2had relatively protection effects. Meanwhile, once daily injection ofC2to STZ-induced diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. Acute feeding studies were evaluated in DIO mice. These results suggested thatC2is a promising agent for further investigation of its potential to treat diabetes patients with obese.
