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.
Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea.
Seungjoon
S
Oh
Minhyung
M
Lee
Kyung Soo
KS
Ko
Suna
S
Choi
Sung Wan
SW
Kim
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018929:Cell Culture Techniques; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000628:therapy*; D005822:Genetic Vectors / Q000008:administration & dosage; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D007275:Injections, Intravenous; D007515:Islets of Langerhans / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D001786:Blood Glucose; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon