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Delivery of two-step transcription amplification exendin-4 plasmid system with arginine-grafted bioreducible polymer in type 2 diabetes animal model

Title
Delivery of two-step transcription amplification exendin-4 plasmid system with arginine-grafted bioreducible polymer in type 2 diabetes animal model
Author
이민형
Keywords
Diabetes; Exendin-4 polyplex; TSTA system; Gene delivery; GLUCAGON-LIKE PEPTIDE-1; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; IN-VIVO; RECEPTOR AGONISTS; INCRETIN MIMETICS; THERAPY; APOPTOSIS; GLP-1
Issue Date
2012-08
Publisher
Elsevier Science B.V., Amsterdam
Citation
Journal of controlled release,Vol.162,No.1 [2012],p9-18
Abstract
Exendin-4, glucagon-like peptide 1 (GLP-1) receptor agonist, is an exocrine hormone, which has potent insulinotropic actions similar to GLP-1 such as stimulating insulin biosynthesis, facilitating glucose concentration dependent insulin secretion, slowing gastric emptying, reducing food intake and stimulating beta-cell proliferation. Exendin-4, also, has a longer half-life than GLP-1, due to its resistance to degradation by dipeptidyl peptidase-IV (DPP-IV). In spite of its many advantages as a therapeutic agent for diabetes, its clinical application is still restricted. Thus, to improve the activity of exendin-4 in vivo, gene therapy system was developed as an alternative method. An exendin-4 expression system was constructed using the two-step transcription amplification (TSTA) system, which is composed of p beta-Gal4-p65 and pUAS-SP-exendin-4 with combining the advantages of signal peptide (SP) in order to facilitate its secretion in ectopic cells or tissue. Arginine-grafted cyctaminebisacrylamide-diaminohexane polymer (ABP) was used as a gene carrier. Increased expression of exendin-4, glucose dependent insulin secretion in NIT-1 insulinoma cells, and high insulin expression in the presence of DPP-IV were evaluated in vitro after delivery of ABP/TSTA-SP-exendin-4. Blood glucose levels in diabetic mice were decreased dramatically from the third day for experimental period after single intravenous administration with ABP/TSTA-SP-exendin-4. The highest insulinotropic effect of exendin-4 was also observed in the ABP/TSTA/SP-exendin-4-treated mice groups, compared with the others groups from the 3rd day after injection. TSTA exendin-4 expression system with SP and ABP polymer has a potential gene therapy for the treatment of type 2 diabetes. (c) 2012 Elsevier B.V. All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0168365912005032?via%3Dihubhttp://hdl.handle.net/20.500.11754/41393
ISSN
0168-3659
DOI
10.1016/j.jconrel.2012.06.010
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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