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口服新型降糖多肽ODA的设计及其口服降糖活性

安东贤, 姚文兵, 高向东, 田浤

安东贤, 姚文兵, 高向东, 田浤. 口服新型降糖多肽ODA的设计及其口服降糖活性[J]. 中国药科大学学报, 2023, 54(4): 511-518. DOI: 10.11665/j.issn.1000-5048.2023032703
引用本文: 安东贤, 姚文兵, 高向东, 田浤. 口服新型降糖多肽ODA的设计及其口服降糖活性[J]. 中国药科大学学报, 2023, 54(4): 511-518. DOI: 10.11665/j.issn.1000-5048.2023032703
AN Dongxian, YAO Wenbing, GAO Xiangdong, TIAN Hong. Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA[J]. Journal of China Pharmaceutical University, 2023, 54(4): 511-518. DOI: 10.11665/j.issn.1000-5048.2023032703
Citation: AN Dongxian, YAO Wenbing, GAO Xiangdong, TIAN Hong. Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA[J]. Journal of China Pharmaceutical University, 2023, 54(4): 511-518. DOI: 10.11665/j.issn.1000-5048.2023032703

口服新型降糖多肽ODA的设计及其口服降糖活性

基金项目: 新疆维吾尔自治区重点研发计划项目资助(No.2020B03003)

Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA

Funds: This study was supported by the Key Research and Development Project of Xinjiang Autonomous Region (No.2020B03003)
  • 摘要: 肠促胰岛素分泌肽胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性促胰岛素释放多肽(GIP)能通过血糖依赖机制促进胰岛素分泌,其特异性结合受体GLP-1R和GIPR是治疗2型糖尿病的良好靶点。以本实验室前期设计的口服降糖多肽OHP2为基础,设计了可口服的新型降糖多肽——ODA。ODA较OHP2的亲脂性提高,在Caco-2细胞中的胞吞能力及跨细胞转运能力更强。ODA保留了OHP2对GLP-1R的激活能力,增强了与GIPR的结合能力。口服低剂量ODA(0.53 mg/kg)即可达到与口服OHP2(1.06 mg/kg)相当的降糖水平。研究结果显示,ODA是治疗2型糖尿病极具潜力的口服药物。
    Abstract: Incretin promotes insulin secretion through a glucose-dependent mechanism, involving glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Therefore, their correspondingly specific receptors GLP-1R and GIPR are suitable targets for the treatment of type 2 diabetes. Based on the oral hypoglycemic peptide OHP2 designed by our team, we further designed a new oral hypoglycemic peptide, ODA to reduce glucose. Compared with OHP2, ODA exhibited better lipophilicity as well as the enhanced endocytosis and transcytosis in Caco-2 cells. In addition, ODA remained the ability to activate GLP-1R and enhanced the binding ability to GIPR. The hypoglycemic efficacy of the low-dose ODA (0.53 mg/kg) is comparable to that of OHP2 (1.06 mg/kg). These results indicated that ODA could be a new oral drug with potential for the treatment of type 2 diabetes.
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出版历程
  • 收稿日期:  2023-03-26
  • 修回日期:  2023-07-11
  • 刊出日期:  2023-08-24

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