| Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice. | |
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MedLine Citation:
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PMID: 18158644 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO(2)) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO(2) was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO(2), while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARgamma-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice. |
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Authors:
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O-J How; T S Larsen; A D Hafstad; A Khalid; E S P Myhre; A J Murray; N T Boardman; M Cole; K Clarke; D L Severson; E Aasum |
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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: Archives of physiology and biochemistry Volume: 113 ISSN: 1381-3455 ISO Abbreviation: Arch. Physiol. Biochem. Publication Date: 2007 Oct-Dec |
Date Detail:
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Created Date: 2007-12-25 Completed Date: 2008-04-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9510153 Medline TA: Arch Physiol Biochem Country: England |
Other Details:
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Languages: eng Pagination: 211-20 Citation Subset: IM |
Affiliation:
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Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway. ole-jakob.how@fagmed.uit.no |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Body Weight / drug effects Cardiovascular Physiological Phenomena / drug effects* Coronary Vessels / drug effects Diabetes Mellitus, Type 2 / drug therapy, physiopathology* Female Heart / drug effects*, physiology, physiopathology Ion Channels / metabolism Ischemia / physiopathology Lipid Metabolism / drug effects Male Mice Mice, Inbred C57BL Mitochondrial Proteins / metabolism Organ Size / drug effects Oxidation-Reduction / drug effects Oxygen Consumption / drug effects RNA, Messenger / genetics, metabolism Reperfusion Injury Thiazolidinediones / pharmacology*, therapeutic use Ventricular Function / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Ion Channels; 0/Mitochondrial Proteins; 0/RNA, Messenger; 0/Thiazolidinediones; 0/mitochondrial uncoupling protein 3; 122320-73-4/rosiglitazone |
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