| Beneficial effects of desferrioxamine on encapsulated human islets--in vitro and in vivo study. | |
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MedLine Citation:
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PMID: 20645943 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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As many as 2000 IEQs (islet equivalent) of encapsulated human islets are required to normalize glucose levels in diabetic mice. To reduce this number, encapsulated islets were exposed to 100 μM desferrioxamine (DFO) prior to transplantation. Cell viability, glucose-induced insulin secretion, VEGF (Vascular endothelial growth factor), HIF-1α (Hypoxia inducible factor-1 alpha), caspase-3 and caspase-8 levels were assessed after exposure to DFO for 12, 24 or 72 h. Subsequently, 1000, 750 or 500 encapsulated IEQs were infused into peritoneal cavity of diabetic mice after 24 h exposure to DFO. Neither viability nor function in vitro was affected by DFO, and levels of caspase-3 and caspase-8 were unchanged. DFO significantly enhanced VEGF secretion by 1.6- and 2.5-fold at 24 and 72 h, respectively, with a concomitant increase in HIF-1α levels. Euglycemia was achieved in 100% mice receiving 1000 preconditioned IEQs, as compared to only 36% receiving unconditioned IEQs (p < 0.001). Similarly, with 750 IEQ, euglycemia was achieved in 50% mice receiving preconditioned islets as compared to 10% receiving unconditioned islets (p = 0.049). Mice receiving preconditioned islets had lower glucose levels than those receiving unconditioned islets. In summary, DFO treatment enhances HIF-1α and VEGF expression in encapsulated human islets and improves their ability to function when transplanted. |
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Authors:
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V Vaithilingam; J Oberholzer; G J Guillemin; B E Tuch |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Volume: 10 ISSN: 1600-6143 ISO Abbreviation: Am. J. Transplant. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-10-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100968638 Medline TA: Am J Transplant Country: United States |
Other Details:
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Languages: eng Pagination: 1961-9 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons. |
Affiliation:
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Department of Pharmacology, University of New South Wales, Sydney, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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