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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2007-2-2
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pubmed:abstractText |
Insulin resistance (IR) precedes the onset of Type 2 diabetes, but its impact on preconditioning against myocardial ischemia-reperfusion injury is unexplored. We examined the effects of diazoxide and ischemic preconditioning (IPC; 5-min ischemia and 5-min reperfusion) on ischemia (30 min)-reperfusion (240 min) injury in young IR Zucker obese (ZO) and lean (ZL) rats. ZO hearts developed larger infarcts than ZL hearts (infarct size: 57.3 +/- 3% in ZO vs. 39.2 +/- 3.2% in ZL; P < 0.05) and also failed to respond to cardioprotection by IPC or diazoxide (47.2 +/- 4.3% and 52.5 +/- 5.8%, respectively; P = not significant). In contrast, IPC and diazoxide treatment reduced the infarct size in ZL hearts (12.7 +/- 2% and 16.3 +/- 6.7%, respectively; P < 0.05). The mitochondrial ATP-activated potassium channel (K(ATP)) antagonist 5-hydroxydecanoic acid inhibited IPC and diazoxide-induced preconditioning in ZL hearts, whereas it had no effect on ZO hearts. Diazoxide elicited reduced depolarization of isolated mitochondria from ZO hearts compared with ZL (73 +/- 9% in ZL vs. 39 +/- 9% in ZO; P < 0.05). Diazoxide also failed to enhance superoxide generation in isolated mitochondria from ZO compared with ZL hearts. Electron micrographs of ZO hearts revealed a decreased number of mitochondria accompanied by swelling, disorganized cristae, and vacuolation. Immunoblots of mitochondrial protein showed a modest increase in manganese superoxide dismutase in ZO hearts. Thus obesity accompanied by IR is associated with the inability to precondition against ischemic cardiac injury, which is mediated by enhanced mitochondrial oxidative stress and impaired activation of mitochondrial K(ATP).
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-hydroxydecanoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Decanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Diazoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxy Acids,
http://linkedlifedata.com/resource/pubmed/chemical/KATP Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Inwardly...,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/uK-ATP-1 potassium channel
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0363-6119
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
292
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R920-6
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17008456-Animals,
pubmed-meshheading:17008456-Decanoic Acids,
pubmed-meshheading:17008456-Diazoxide,
pubmed-meshheading:17008456-Hydroxy Acids,
pubmed-meshheading:17008456-Immunoblotting,
pubmed-meshheading:17008456-Insulin Resistance,
pubmed-meshheading:17008456-Ischemic Preconditioning, Myocardial,
pubmed-meshheading:17008456-KATP Channels,
pubmed-meshheading:17008456-Male,
pubmed-meshheading:17008456-Membrane Potentials,
pubmed-meshheading:17008456-Microscopy, Electron,
pubmed-meshheading:17008456-Mitochondria, Heart,
pubmed-meshheading:17008456-Mitochondrial Membranes,
pubmed-meshheading:17008456-Myocardial Reperfusion Injury,
pubmed-meshheading:17008456-Obesity,
pubmed-meshheading:17008456-Potassium Channel Blockers,
pubmed-meshheading:17008456-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:17008456-Rats,
pubmed-meshheading:17008456-Rats, Zucker,
pubmed-meshheading:17008456-Reactive Oxygen Species,
pubmed-meshheading:17008456-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17008456-Superoxide Dismutase,
pubmed-meshheading:17008456-Vasodilator Agents
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pubmed:year |
2007
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pubmed:articleTitle |
Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance.
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pubmed:affiliation |
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Hanes 1050, Medical Center Blvd, Winston-Salem, NC 27157, USA. pkatakam@wfubmc.edu
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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