| Intra-arterial targeted islet-specific expression of Sirt1 protects β cells from streptozotocin-induced apoptosis in mice. | |
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MedLine Citation:
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PMID: 20842108 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gene therapy provides a promising approach to curing diabetes. However, an effective route for islet-specific targeting has yet to be established. Toward this end, the pancreatic blood circulation system in Balb/c mice was determined by the injection of rhodamine-containing beads. The efficiency of islet targeting was then measured by the injection of adenoviral vectors carrying a green fluorescence gene via the celiac trunk (C.T.). The results showed that >95% of islets and about 60% of β cells within the pancreatic body and tail could be labeled 3 days after surgery. α-Cell labeling was not as efficient, whereas labeling of nonendocrine tissues was barely detectable. For proof of principle, adenoviral vectors carrying a Sirtuin transgene were injected similarly to test the islet protection effect in the streptozotocin (STZ)-induced type 1 diabetic model. The results demonstrated that overexpression of Sirtuin in STZ-treated mice reduced the level of β-cell death and extent of glucose intolerance. This study reports on efficient islet-specific targeting by using adenoviral injection. This procedure could be invaluable to the treatment of diabetes and the study of islet biology. |
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Authors:
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Mi-mi Tang; Qin-e Zhu; Wen-zhu Fan; Shui-li Zhang; Di-zheng Li; Li-zhong Liu; Miao Chen; Mei Zhang; Jing Zhou; Chi-ju Wei |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-14 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: 19 ISSN: 1525-0024 ISO Abbreviation: Mol. Ther. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: 2011-04-14 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 60-6 Citation Subset: IM |
Affiliation:
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Multidisciplinary Research Center, Shantou University, Shantou, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Animals Apoptosis / drug effects* Blood Glucose / metabolism Diabetes Mellitus, Experimental / metabolism, pathology, therapy* Gene Therapy / methods* Genetic Vectors / administration & dosage, genetics Glucose Intolerance / therapy Green Fluorescent Proteins / genetics Injections, Intra-Arterial Insulin-Secreting Cells / drug effects*, metabolism, pathology Mice Mice, Inbred BALB C Molecular Targeted Therapy / methods Pancreas / blood supply, drug effects, metabolism Rhodamines / diagnostic use Sirtuin 1 / biosynthesis*, genetics Streptozocin / pharmacology* Transgenes |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Rhodamines; 147336-22-9/Green Fluorescent Proteins; 18883-66-4/Streptozocin; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1 |
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