1. ¹Center 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, UT 84112-5820, USA
2. ²Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea
3. ³Department of Bioengineering, College of Engineering, Hanyang University, Seoul 177-791, Korea

Correspondence: Sung Wan Kim, Fax: +1 801 581 7848. E-mail: rburns@pharm.utah.edu

Received 30 November 2004; Revised 22 March 2005; Accepted 30 March 2005.

Abstract

Glucagon-like peptide-1 (GLP-1) is a 30-amino-acid hormone produced by intestinal L cells. It has been proposed that GLP-1 can be used as a new treatment for type 2 diabetes mellitus because it acts to augment insulin secretion and its effectiveness is maintained in type 2 diabetic patients. Despite its many remarkable advantages as a therapeutic agent for diabetes, GLP-1 is not immediately clinically applicable because of its extremely short half-life. One way to overcome this drawback is GLP1 gene delivery, which enables GLP-1 production in the body. In this study, the effect of GLP1 gene delivery was evaluated both in vitro and in vivo using a new plasmid constructed with a GLP1 (7–37) cDNA. The expression of the GLP1 gene was driven by a SV40 promoter/enhancer. To increase the expression level of GLP-1, nuclear factor B binding sites were introduced. The in vitro results showed expression of GLP-1 and in vitro activity of GLP-1, which is a glucose-dependent insulinotropic action. A single systemic administration of polyethyleneimine/pSIGLP1NFB complex into DIO mice resulted in increasing insulin secretion and decreasing blood glucose levels for a duration longer than 2 weeks.