59 0

Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets

Title
Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets
Author
이민형
Keywords
glucagon-like peptide-1; islet; transplantation
Issue Date
2013-01
Publisher
Wiley-Blackwell
Citation
Transplant International, 2013, 26(4), P.443-452
Abstract
Glucagon-like peptide-1 (GLP-1) stimulates cell proliferation and has anti-apoptotic effects on pancreatic islet cells. In our previous study, the transduction of mouse islets with a recombinant adenovirus containing GLP-1 cDNA enhanced islet graft survival. In this study, we sought to deliver the GLP-1 gene using a nonviral vector, which raises fewer safety issues in clinical application. We constructed a plasmid, p-SP-GLP-1, in which a secretion signal peptide (SP) was inserted to increase GLP-1 secretion, and transfected mouse islets using the nonviral carrier Effectene. Transfection of p-SP-GLP-1 induced a significant increase in bioactive GLP-1 levels in islet cultures. Islets transfected with p-SP-GLP-1 were protected from H2O2-induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in p-SP-GLP-1-transfected islets. Diabetic syngeneic mice transplanted under the kidney capsule with a marginal mass of p-SP-GLP-1-transfected islets rapidly became normoglycemic, with 88% of recipients being normoglycemic at 30days post-transplantation compared with 52% of mice that received p-transfected islet grafts (P˂0.05). Islet grafts retrieved 7days after transplantation revealed that the p-SP-GLP-1-transfected group had significantly more Ki67-positive cells as compared with the p-transfected group. In conclusion, delivery of a plasmid containing a secretion SP and GLP-1 cDNA using a nonviral carrier leads to efficient secretion of GLP-1 in mouse islet cells, enhances islet cell survival during the early post-transplant period, and improves islet transplantation outcome.
URI
https://onlinelibrary.wiley.com/doi/abs/10.1111/tri.12052http://hdl.handle.net/20.500.11754/50448
ISSN
0934-0874
DOI
10.1111/tri.12052
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE