Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets
- Authors
- Chae, Hee Young; Lee, Minhyung; Hwang, Hyo Jeong; Kim, Hyun Ah; Kang, Jun Goo; Kim, Chul Sik; Lee, Seong Jin; Ihm, Sung-Hee
- Issue Date
- Apr-2013
- Publisher
- WILEY
- Keywords
- glucagon-like peptide-1; islet; transplantation
- Citation
- TRANSPLANT INTERNATIONAL, v.26, no.4, pp.443 - 452
- Indexed
- SCIE
SCOPUS
- Journal Title
- TRANSPLANT INTERNATIONAL
- Volume
- 26
- Number
- 4
- Start Page
- 443
- End Page
- 452
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/163076
- DOI
- 10.1111/tri.12052
- ISSN
- 0934-0874
- 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.
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