Document Detail

Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice.
MedLine Citation:
PMID:  18158644     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of physiology and biochemistry     Volume:  113     ISSN:  1381-3455     ISO Abbreviation:  Arch. Physiol. Biochem.     Publication Date:    2007 Oct-Dec
Date Detail:
Created Date:  2007-12-25     Completed Date:  2008-04-16     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9510153     Medline TA:  Arch Physiol Biochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  211-20     Citation Subset:  IM    
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MeSH Terms
Blood Glucose / metabolism
Body Weight / drug effects
Cardiovascular Physiological Phenomena / drug effects*
Coronary Vessels / drug effects
Diabetes Mellitus, Type 2 / drug therapy,  physiopathology*
Heart / drug effects*,  physiology,  physiopathology
Ion Channels / metabolism
Ischemia / physiopathology
Lipid Metabolism / drug effects
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
Grant Support
PS/02/002/14893//British Heart Foundation; RG/07/004/22659//British Heart Foundation
Reg. No./Substance:
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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