Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA

AN Dongxian; YAO Wenbing; GAO Xiangdong; TIAN Hong

doi:10.11665/j.issn.1000-5048.2023032703

Journal of China Pharmaceutical University > 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

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Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA

Jiangsu Provincial Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the Key Research and Development Project of Xinjiang Autonomous Region (No.2020B03003)

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Received Date: March 26, 2023
Revised Date: July 11, 2023

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Abstract

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.
- incretin,
- glucagon-like peptide-1,
- glucose-dependent insulinotropic peptide,
- type 2 diabetes,
- oral hypoglycemic activity

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