GLP-1 gene delivery for the treatment of type 2 diabetes.
Glucagon-like peptide-1 (GLP-1) is a potent insulinotrophic hormone, which makes GLP-1 an attractive candidate for the treatment of type 2 diabetes. However, the short plasma half-life of the active forms of GLP-1 poses an obstacle to the sustained delivery of this peptide. In this study, we evaluated the effect of GLP-1 gene delivery both in vitro and in vivo using a new plasmid constructed with a modified GLP-1 (7-37) cDNA. This cDNA contains a furin cleavage site between the start codon and the GLP-1 coding region. The expression of the GLP-1 gene was driven by a chicken beta-actin promoter (pbetaGLP1). The level of the GLP-1 mRNA was evaluated by RT-PCR 24 h after transfection. The in vitro results showed a dose-dependent expression of GLP-1. Coculture assay of the GLP-1 plasmid-transfected cells with isolated rat islet cells demonstrated that GLP-1 increased insulin secretion by twofold, compared to controls during a hyperglycemic challenge. A single injection of polyethyleneimine/pbetaGLP1 complex into ZDF rats resulted in increasing insulin secretion and decreasing blood glucose level that was maintained for 2 weeks. This GLP-1 gene delivery system may provide an effective and safe treatment modality for type 2 diabetes.[1]References
- GLP-1 gene delivery for the treatment of type 2 diabetes. Oh, S., Lee, M., Ko, K.S., Choi, S., Kim, S.W. Mol. Ther. (2003) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg