GLP-1 gene delivery for the treatment of type 2 diabetes

Mol Ther. 2003 Apr;7(4):478-83. doi: 10.1016/s1525-0016(03)00036-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cell Culture Techniques
  • Cell Line
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / therapy*
  • Genetic Vectors / administration & dosage
  • Glucagon / genetics*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Injections, Intravenous
  • Islets of Langerhans / metabolism
  • Peptide Fragments / genetics*
  • Peptide Fragments / metabolism
  • Plasmids / genetics
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • Rats


  • Blood Glucose
  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon