Document Detail


Functional enhancement of beta cells in transplanted pancreatic islets by secretion signal peptide-linked exendin-4 gene transduction.
MedLine Citation:
PMID:  22306337     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study assessed whether the newly designed exendin-4 (Ex-4) gene with highly releasable characteristics could enhance the beta cell function, thereby attenuating the essential islet mass required to cure diabetes. We constructed a lentivirus system encoding for a highly releasable secretion signal peptide, the peptide linked Ex-4 (SP-Ex-4) gene. After the transduction of lentivirus encoding for SP-Ex-4 (LV-SP-Ex-4) gene into the islets, the therapeutic effects of Ex-4 secreted were evaluated by conducting glucose-stimulated insulin secretion and cytokine- or hypoxia-induced apoptosis. Additionally, the effect of reduced islet numbers for transplantation was evaluated via in vivo models. The transduction of LV-SP-Ex-4 gene did not affect the viability of islets. In diabetic animal models, 50 islets expressing Ex-4 were transplanted to cure the diabetic nude mice, whereas at least 150 untransduced islets had to be transplanted to cure the diabetic nude mice. When the transduced islets were transplanted into diabetic immunocompetent mice, the survival rate of the mice was 18.0±4.9days; however, when the untransduced islets were transplanted, they were rejected within 10.0±0.6days. Therefore, the highly releasable Ex-4 could enhance the beta cell function with slightly enhanced viability of transplanted islets, presenting as a potential technology for overcoming islet shortage.
Authors:
Jee-Heon Jeong; Simmyung Yook; Yoonsuk Jung; Bok-Hyeon Im; Minhyung Lee; Cheol-Hee Ahn; Dong Yun Lee; Youngro Byun
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-27
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  -     ISSN:  1873-4995     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-2-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
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