Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA

VernacularTitle:口服新型降糖多肽ODA的设计及其口服降糖活性
Author: Dongxian AN ¹ ; Wenbing YAO ; Xiangdong GAO ; Hong TIAN
Author Information

1. 中国药科大学生命科学与技术学院江苏省生物药物成药性研究重点实验室
Publication Type:Journal Article
Keywords: ncretin; glucagon-like peptide-1; glucose-dependent insulinotropic peptide; type 2 diabetes; oral hypoglycemic activity
From: Journal of China Pharmaceutical University 2023;54(4):511-518
CountryChina
Language:Chinese
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.