Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets.
Transpl Int
; 26(4): 443-52, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23346912
Glucagon-like peptide-1 (GLP-1) stimulates cell proliferation and has anti-apoptotic effects on pancreatic islet ß 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, pß-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 pß-SP-GLP-1 induced a significant increase in bioactive GLP-1 levels in islet cultures. Islets transfected with pß-SP-GLP-1 were protected from H2 O2 -induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in pß-SP-GLP-1-transfected islets. Diabetic syngeneic mice transplanted under the kidney capsule with a marginal mass of pß-SP-GLP-1-transfected islets rapidly became normoglycemic, with 88% of recipients being normoglycemic at 30 days post-transplantation compared with 52% of mice that received pß-transfected islet grafts (P < 0.05). Islet grafts retrieved 7 days after transplantation revealed that the pß-SP-GLP-1-transfected group had significantly more Ki67-positive cells as compared with the pß-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Señales de Clasificación de Proteína
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Transfección
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Trasplante de Islotes Pancreáticos
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Péptido 1 Similar al Glucagón
Límite:
Animals
Idioma:
En
Revista:
Transpl Int
Asunto de la revista:
TRANSPLANTE
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Suiza