Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes.
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 kappaB 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/pSIGLP1NFkappaB complex into DIO mice resulted in increasing insulin secretion and decreasing blood glucose levels for a duration longer than 2 weeks.
Choi
Suna
S
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, UT 84112-5820, USA.
Oh
Seungjoon
S
Lee
Minhyung
M
Kim
Sung Wan
SW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000628:therapy*; D005822:Genetic Vectors; D005934:Glucagon; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000627:therapeutic use*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D011498:Protein Precursors / Q000008:administration & dosage*
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon