Document Detail


Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression.
MedLine Citation:
PMID:  20850803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Myocardial infarction leads to contractile dysfunction. In patients with diabetes, impaired contractility has been associated with the loss of insulin effects and mitochondrial dysfunction. We assessed cardiac insulin sensitivity and mitochondrial and contractile function in rats after ligation of the left coronary artery. METHODS: At 2 weeks after left coronary artery ligation, we performed echocardiography in vivo and assessed the substrate use and insulin response in the isolated working heart and the regulation of insulin (Akt, glucose transporter type 4) and mitochondrial signaling (p38 mitogen-activated protein kinase, peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A) using polymerase chain reaction and Western blotting. RESULTS: The infarcted hearts were dilated and had a reduced ejection fraction (ejection fraction < 50%). The basal glucose oxidation was preserved, but the fatty acid oxidation was significantly reduced. Insulin's effect on substrate oxidation was significantly impaired for both the decrease in fatty acid oxidation and the increase in glucose oxidation. However, insulin-stimulated glucose uptake was normal in the infarcted hearts, consistent with normal insulin-induced phosphorylation of Akt and unchanged mRNA expression of glucose transporter type 4. The impaired oxidative response to insulin was associated with reduced mRNA expression of the genes regulating fatty acid oxidation (long-chain-acyl-coenzyme A dehydrogenase, carnitine palmitoyltransferase 1, peroxisome proliferator-activated receptor-α) and mitochondrial biogenesis (mitochondrial transcription factor A). Although mRNA expression of the mitochondrial master regulator peroxisome proliferator-activated receptor-γ coactivator 1α was normal in the infarcted hearts, the protein expression of its post-transcriptional activator, p38 mitogen-activated protein kinase, was significantly reduced. CONCLUSIONS: Myocardial infarction in rats caused partial insulin resistance at the level of substrate oxidation, which was associated with mitochondrial and cardiac contractile dysfunction. Mitochondrial dysfunction was characterized by a reduced capacity to oxidize fatty acids and might have resulted from impaired mitochondrial biogenesis through the lack of p38 mitogen-activated protein kinase.
Authors:
Paulo A Amorim; T Dung Nguyen; Yasushige Shingu; Michael Schwarzer; Friedrich W Mohr; Andrea Schrepper; Torsten Doenst
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-17
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  140     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1160-7     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2010. Published by Mosby, Inc.
Affiliation:
Department of Cardiac Surgery, University of Leipzig Heart Center, Leipzig, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acyl-CoA Dehydrogenase, Long-Chain / genetics
Animals
Blood Glucose / metabolism
Carnitine O-Palmitoyltransferase / genetics
Disease Models, Animal
Fatty Acids / metabolism*
Gene Expression Regulation
Glucose Transporter Type 4 / genetics,  metabolism
Insulin / metabolism*
Insulin Resistance* / genetics
Male
Mitochondria, Heart / metabolism*
Mitochondrial Proteins / genetics,  metabolism*
Myocardial Contraction* / genetics
Myocardial Infarction / genetics,  metabolism*,  physiopathology,  ultrasonography
Myocardium / metabolism*
Oxidation-Reduction
PPAR alpha / genetics
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
RNA, Messenger / metabolism
RNA-Binding Proteins / genetics
Rats
Rats, Sprague-Dawley
Time Factors
Transcription Factors / genetics
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids; 0/Glucose Transporter Type 4; 0/Mitochondrial Proteins; 0/PPAR alpha; 0/Ppargc1a protein, rat; 0/RNA, Messenger; 0/RNA-Binding Proteins; 0/Slc2a4 protein, rat; 0/Tfam protein, rat; 0/Transcription Factors; 11061-68-0/Insulin; EC 1.3.99.13/Acyl-CoA Dehydrogenase, Long-Chain; EC 2.3.1.21/Carnitine O-Palmitoyltransferase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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