Related Experiment Video
Updated: Sep 24, 2025

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
Novel mono-lipidated dimeric glucagon-like peptide-1 receptor agonist with improved long-acting and hypoglycemic
Lidan Sun1, Jing Han2, Xinyu Chen2
1Integrated Medicine Research Center for Neurological Rehabilitation, College of Medicine, Jiaxing University Jiaxing 314001 PR China.
Abstract:
Dimerization is a useful tool to boost ligand-receptor interaction. Both lipidation and dimerization effectively prolong the short half-life (t 1/2) of peptides by facilitating binding with serum albumin and increasing hydrodynamic size. Here, we described two novel GLP-1 conjugates with high glucagon-like peptide-1 (GLP-1) receptor activation potencies, dimerized GLP-1 (Di-GLP-1) and lipidated Di-GLP-1 (Lip-Di-GLP-1). Di-GLP-1 and Lip-Di-GLP-1 were prepared through cysteine-maleimide specific coupling reactions using Gly8-Cys31-GLP-1, bis-maleimide amine, and activated palmitic acid. The receptor activation potencies of Di-GLP-1 and Lip-Di-GLP-1 were 13.6-fold and 9.5-fold higher than GLP-1, respectively. The in vivo hypoglycemic and insulinotropic activities of Di-GLP-1 and Lip-Di-GLP-1 were also better than GLP-1 in db/db mice. Furthermore, Lip-Di-GLP-1 was found to have greater circulating t 1/2 than synthesized liraglutide by 1.8-fold. Accordingly, the improved pharmacokinetic profiles of Lip-Di-GLP-1 resulted in protracted antidiabetic effects as confirmed by hypoglycemic duration test. Moreover, Lip-Di-GLP-1 administered in mice potently inhibits gastric emptying and reduce food intake. Chronic Lip-Di-GLP-1 treatment in db/db mice resulted in significant improvements in food intake, body weight, pancreatic function and corrected hyperglycemia, which was more effective than synthesized liraglutide. Our research indicated that combined dimerization and lipidation were effectively applied to GLP-1, and the preclinical results suggested the potential usage of Lip-Di-GLP-1 as a long-acting antidiabetic agent.
Related Concept Videos
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Oral Hypoglycemic Agents: Glinides
Dipeptidyl Peptidase 4 Inhibitors
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
Oral Hypoglycemic Agents: Biguanides and Glitazones
Hypoglycemia and Glucagon

