| Long-term, antidiabetogenic effects of GLP-1 gene therapy using a double-stranded, adeno-associated viral vector. | |
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MedLine Citation:
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PMID: 20720576 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Diabetes is characterized by insulin resistance and a reduction in insulin secretion, leading to progressive β-cell failure and loss of β-cell mass. Its central therapeutic issues are how to restore glucose responsiveness of β-cells to normal and counteract defects in insulin secretion. Native glucagon-like peptide-1 (GLP-1), which makes β-cells competent and diabetic β-cells specifically more sensitive to glucose, has a major drawback of rapid inactivation. In this study, we describe the construction and analysis of a GLP-1 plasmid and double-stranded, adeno-associated viral (dsAAV) expression vector to overcome both the rapid degradation of native GLP-1 and limitations of gene therapy using standard single-stranded AAV. Our study results demonstrate that fasting blood glucose levels of db/db obese mice decreased significantly up to 4 months after a single injection of dsAAV GLP-1, and both insulin and circulating GLP-1 levels increased in dsAAV GLP-1-infected mice. These results demonstrate that dsAAV GLP-1 has long-term, efficient transgene expression with minimal toxicity and cellular immune responses. This study suggests that GLP-1 produced by dsAAV may be an alternative to the continuous infusions required for GLP-1 peptide therapy or daily injections of GLP-1. |
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Authors:
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S H Choi; H C Lee |
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Publication Detail:
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Type: Journal Article Date: 2010-08-19 |
Journal Detail:
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Title: Gene therapy Volume: 18 ISSN: 1476-5462 ISO Abbreviation: Gene Ther. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: England |
Other Details:
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Languages: eng Pagination: 155-63 Citation Subset: IM |
Affiliation:
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Department of Endocrinology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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