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• W2016267751 abstract "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." @default.
• W2016267751 created "2016-06-24" @default.
• W2016267751 creator A5038803419 @default.
• W2016267751 creator A5070155546 @default.
• W2016267751 date "2010-08-19" @default.
• W2016267751 modified "2023-09-23" @default.
• W2016267751 title "Long-term, antidiabetogenic effects of GLP-1 gene therapy using a double-stranded, adeno-associated viral vector" @default.
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• W2016267751 doi "https://doi.org/10.1038/gt.2010.119" @default.
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