| Reduced CGP12177 binding to cardiac β-adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats. | |
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MedLine Citation:
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PMID: 21831645 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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INTRODUCTION: Abnormal sympathetic nervous system and β-adrenoceptor (β-AR) signaling is associated with diabetes. [(3)H]CGP12177 is a nonselective β-AR antagonist that can be labeled with carbon-11 for positron emission tomography. The aim of this study was to examine the suitability of this tracer for evaluation of altered β-AR expression in diabetic rat hearts. METHODS: Ex vivo biodistribution with [(3)H]CGP12177 was carried out in normal Sprague-Dawley rats for evaluation of specific binding and response to continuous β-AR stimulation by isoproterenol. In a separate group, high-fat-diet feeding imparted insulin resistance and a single intraperitoneal injection of streptozotocin (STZ) or vehicle evoked hyperglycemia (blood glucose >11 mM). [(3)H]CGP12177 biodistribution was assessed at 2 and 8 weeks post-STZ to measure β-AR binding in heart, 30 min following tracer injection. Western blotting of β-AR subtypes was completed in parallel. RESULTS: Infusion of isoproterenol over 14 days did not affect cardiac binding of [(3)H]CGP12177. Approximately half of rats treated with STZ exhibited sustained hyperglycemia and progressive hypoinsulinemia. Myocardial [(3)H]CGP12177 specific binding was unchanged at 2 weeks post-STZ but significantly reduced by 30%-40% at 8 weeks in hyperglycemic but not euglycemic STZ-treated rats compared with vehicle-treated controls. Western blots supported a significant decrease in β(1)-AR in hyperglycemic rats. CONCLUSIONS: Reduced cardiac [(3)H]CGP12177 specific binding in the presence of sustained hyperglycemia corresponds to a decrease in relative β(1)-AR expression. These data indirectly support the use of [(11)C]CGP12177 for assessment of cardiac dysfunction in diabetes. |
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Authors:
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James T Thackeray; Maryam Parsa-Nezhad; Miran Kenk; Stephanie L Thorn; Maria Kolajova; Rob S B Beanlands; Jean N Dasilva |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-8 |
Journal Detail:
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Title: Nuclear medicine and biology Volume: - ISSN: 1872-9614 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y4W7; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, Canada K1H8M5. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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