Novel GLP-1(28-36) amide-derived hybrid peptide A3 with weight loss and hypoglycemic activities

Chen Wang; Binbin Gong; Qianqian Zhu; Jing Han; Lidan Sun

doi:10.1016/j.ejphar.2023.176200

Novel GLP-1(28-36) amide-derived hybrid peptide A3 with weight loss and hypoglycemic activities

Eur J Pharmacol. 2023 Dec 15:961:176200. doi: 10.1016/j.ejphar.2023.176200. Epub 2023 Nov 16.

Authors

Chen Wang¹, Binbin Gong², Qianqian Zhu¹, Jing Han³, Lidan Sun⁴

Affiliations

¹ Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China.
² Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310000, PR China.
³ School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China.
⁴ Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China. Electronic address: slidan89@zjxu.edu.cn.

PMID: 37979828
DOI: 10.1016/j.ejphar.2023.176200

Abstract

Glucagon-like peptide-1 (GLP-1) has gained much attention in the last decade for the treatment of type 2 diabetes. Accumulating evidence indicates that some metabolites of GLP-1 have biological activities that might contribute to the pleiotropic effects of GLP-1 independent of the GLP-1 receptor. The hypoglycemic and weight-reducing effects of the reported metabolites and modifications still need to be confirmed. In this study, we started from the C-terminal nonapeptide GLP-1(28-36) amide and developed a series of GLP-1(28-36) amide-derived hybrid peptides. Our findings of biological activity evaluation in INS-1 cells, streptozotocin-induced diabetic and diet-induced obesity mice confirmed a novel hybrid peptide, A3, and provided a new perspective in the development of new drugs from peptide metabolites.

Keywords: Glucagon-like peptide-1; Metabolite; Obesity; Type 2 diabetes.

MeSH terms

Amides / pharmacology
Amides / therapeutic use
Animals
Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / metabolism
Glucagon-Like Peptide 1* / metabolism
Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use
Mice
Peptide Fragments / pharmacology
Peptides / pharmacology
Peptides / therapeutic use
Weight Loss

Substances

Glucagon-Like Peptide 1
Hypoglycemic Agents
Amides
Peptides
Glucagon-Like Peptide-1 Receptor
Peptide Fragments