The chronic administration of two novel long-acting Xenopus glucagon-like peptide-1 analogs xGLP159 and xGLP296 potently improved systemic metabolism and glycemic control in rodent models
The chronic administration of two novel long-acting Xenopus glucagon-like peptide-1 analogs xGLP159 and xGLP296 potently improved systemic metabolism and glycemic control in rodent models
复制标题
两种新型长效非洲爪蟾胰高血糖素样肽-1类似物 xGLP159 和 xGLP296 的长期给药可有效改善啮齿动物模型的全身代谢和血糖控制
DOI：
10.1096/fj.201801479r
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发表时间：
2019-06-01
期刊：
影响因子：
4.8
通讯作者：
Li, Chenglin
中科院分区：
文献类型：
--
作者：
Han, Jing;Meng, Tingting;Li, Chenglin
本文报道了2种新的爪蟾胰高血糖素样肽-1（xGLP-1）类似物xGLP 159和xGLP 296，在啮齿类动物中评价了它们对代谢功效和血糖控制的治疗作用。在人胚肾293细胞上研究了xGLP 159和xGLP 296的体外效力。在昆明癌症研究所和糖尿病（db/db）小鼠中评估xGLP 159和xGLP 296的急性降糖和促胰岛素作用。在Sprague-Dawley（SD）大鼠中证实了xGLP 159和xGLP 296的药代动力学特征，并在db/db小鼠中评价了其长效降糖和厌食作用。在饮食诱导的肥胖（DIO）小鼠和db/db小鼠中评价了xGLP 159和xGLP 296的长期治疗作用。结果表明，xGLP 159和xGLP 296表现出与利拉鲁肽相当的受体激活效力、降血糖作用和促胰岛素活性。SD大鼠中xGLP 159和xGLP 296的半衰期延长（分别为5.1和5.8 h）导致db/db小鼠中抗db/db持续时间延长。给予xGLP 159和xGLP 296三周使DIO小鼠的葡萄糖耐量和肥胖正常化。此外，xGLP 159和xGLP 296治疗11周可纠正db/db小鼠的高血糖症并改善胰腺功能。这些临床前研究支持xGLP 159和xGLP 296作为治疗代谢性疾病的有希望的候选药物。汉，J.，孟，T.，陈旭，汉，Y.，傅，J.，Zhou，F.，中国科学院院士，费，Y.，Li，C.两种新型长效爪蟾胰高血糖素样肽-1类似物xGLP 159和xGLP 296的长期给药有效改善了啮齿动物模型的全身代谢和血糖控制。
We here reported 2 novel Xenopus glucagon-like peptide-1 (xGLP-1) analogs, xGLP159 and xGLP296, whose therapeutic effects on metabolic efficacy and glycemic control were evaluated in rodents. The in vitro potency of xGLP159 and xGLP296 were investigated on human embryonic kidney 293 cells. The acute glucose-lowering and insulinotropic effects of xGLP159 and xGLP296 were assessed in the Institute of Cancer Research, Kunming, and diabetic (db/db) mice. The pharmacokinetic profiles of xGLP159 and xGLP296 were confirmed on Sprague-Dawley (SD) rats and their long-acting hypoglycemic and anorectic effects were evaluated in db/db mice. Chronic treatment effects of xGLP159 and xGLP296 were evaluated in diet-induced obese (DIO) mice and db/db mice. The results showed that xGLP159 and xGLP296 exhibited comparable receptor activation potency, hypoglycemic effect, and insulinotropic activity to liraglutide. The enhanced half-lives of xGLP159 and xGLP296 in SD rats (5.1 and 5.8 h, respectively) resulted in prolonged anti-db/db durations in db/db mice. Three weeks' administration of xGLP159 and xGLP296 normalized glucose tolerance and adiposity in DIO mice. Furthermore, 11-wk treatment of xGLP159 and xGLP296 corrected hyperglycemia and improved pancreatic function in db/db mice. These preclinical studies supported xGLP159 and xGLP296 as promising candidates for the treatment of metabolic diseases.-Han, J., Meng, T., Chen, X., Han, Y., Fu, J., Zhou, F., Fei, Y., Li, C. The chronic administration of two novel long-acting Xenopus glucagon-like peptide-1 analogs xGLP159 and xGLP296 potently improved systemic metabolism and glycemic control in rodent models.