Effect of glucagon-like peptide-1 gene expression on graft function in mouse islet transplantation
- Authors
- Chae, Hee Young; Kang, Jun Goo; Kim, Chul Sik; Lee, Seong Jin; Lee, Minhyung; Kang, Dongchul; Jun, Hee-Sook; Ihm, Sung-Hee
- Issue Date
- Feb-2012
- Publisher
- WILEY
- Keywords
- glucagon-like peptide-1 (GLP-1); islet; transplantation
- Citation
- TRANSPLANT INTERNATIONAL, v.25, no.2, pp.242 - 249
- Indexed
- SCIE
SCOPUS
- Journal Title
- TRANSPLANT INTERNATIONAL
- Volume
- 25
- Number
- 2
- Start Page
- 242
- End Page
- 249
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/166333
- DOI
- 10.1111/j.1432-2277.2011.01394.x
- ISSN
- 0934-0874
- Abstract
- This study investigated the effect of local glucagon-like peptide-1 (GLP-1) production within mouse islets on cytoprotection in vitro and in vivo by gene transfer of GLP-1. Transduction of recombinant adenovirus vector expressing GLP-1 (rAd-GLP-1) induced a significant increase in bioactive GLP-1 in the mouse islet culture, whereas transduction with adenovirus vector expressing beta-galactosidase (rAd-LacZ), as a control, had no effect on GLP-1 secretion. Islets transduced with rAd-GLP-1 were protected from H2O2-induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in rAd-GLP-1-transduced islets. When transplanted under the kidney capsule of diabetic syngeneic mice, islet grafts retrieved 4 or 7 days after transplantation revealed that the rAd-GLP-1-transduced group had significantly more Ki67-positive cells as compared with the rAd-LacZ-transduced group. Regarding blood glucose control, diabetic mice transplanted with a marginal mass of rAd-GLP-1-transduced islets became normoglycemic more rapidly and 78% of the recipients were normoglycemic at 35 days post-transplant, whereas only 48% of the mice transplanted with rAd-LacZ-transduced islets were normoglycemic (P < 0.05). In conclusion, delivery of the GLP-1 gene to islets enhanced islet cell survival during the early post-transplant period, and preserved islet mass and functions over time in the transplants.
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