GLP-1 gene delivery for the treatment of type 2 diabetes |
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Institution: | 1. Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea;2. Clinical Research Center, College of Medicine, Inha University, Inchon, Korea;3. Department of Internal Medicine, College of Medicine, Inje University, Seoul, Korea;4. Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Biochemical Polymer Research Building, RM201, Salt Lake City, Utah 84112, USA |
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Abstract: | 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 β-actin promoter (pβGLP1). 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/pβGLP1 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. |
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Keywords: | GLP-1 gene therapy diabetes mellitus type 2 |
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