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- Title
Poly-GLP-1, a novel long-lasting glucagon-like peptide-1 polymer, ameliorates hyperglycaemia by improving insulin sensitivity and increasing pancreatic beta-cell proliferation.
- Authors
Ma, X.; Hui, H.; Liu, Z.; He, G.; Hu, J.; Meng, J.; Guan, L.; Luo, X.
- Abstract
Aim: The clinical value of glucagon-like peptide-1 (GLP-1) is restricted because of its short half-life. To overcome this limitation, a new polymer of GLP-1 was developed by prodrug strategy, termed Poly-GLP-1, and its pharmacological properties were investigated. Methods: The in vitro release kinetics of GLP-1 from Poly-GLP-1 was analysed by Western blot. Plasma GLP-1 levels following a single administration of Poly-GLP-1 were determined by enzyme-linked immunosorbent assay. The in vitro effects of Poly-GLP-1 were evaluated using isolated pancreatic islets. The acute effects on glycaemic control and food intake were investigated in C57BL/6J mice s.c. administered with Poly-GLP-1. The chronic effects of Poly-GLP-1 on glycaemic control were further assessed in C57BL/6J and db/db mice treated twice daily for 6 weeks. Results: Pro-GLP-1 dose dependently increased insulin secretion and decreased glucose, but did not exhibit the insulinotropic action in isolated pancreatic islets without plasma. The glucose-lowering actions of Poly-GLP-1 (3 nmol/kg) remained no less than 12 h after a single injection. Poly-GLP-1 caused a durable restoration of glycaemic control, food intake and body weight gain in db/db mice following 6-week administration. The chronic treatment with Poly-GLP-1 improved glucose tolerance and insulin sensitivity and increased β-cell mass and proliferation in db/db mice. There was little effect on normal mice treated in the same manner. Conclusions: Our results indicated that Poly-GLP-1, a novel GLP-1 polymer, has long-lasting and potent effects on glycaemic control in vivo, and these beneficial effects may be because of improvement of insulin sensitivity and promotion of islet growth and function.
- Subjects
GLUCAGON-like peptide 1; PANCREATIC beta cells; CELL proliferation; POLYMERS; PRODRUGS; OBESITY; MICE
- Publication
Diabetes, Obesity & Metabolism, 2009, Vol 11, Issue 10, p953
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2009.01070.x