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Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression.
J Thorac Cardiovasc Surg. 2010 Nov; 140(5):1160-7.JT

Abstract

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+Show Affiliations

Department of Cardiac Surgery, University of Leipzig Heart Center, Leipzig, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20850803

Citation

Amorim, Paulo A., et al. "Myocardial Infarction in Rats Causes Partial Impairment in Insulin Response Associated With Reduced Fatty Acid Oxidation and Mitochondrial Gene Expression." The Journal of Thoracic and Cardiovascular Surgery, vol. 140, no. 5, 2010, pp. 1160-7.
Amorim PA, Nguyen TD, Shingu Y, et al. Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression. J Thorac Cardiovasc Surg. 2010;140(5):1160-7.
Amorim, P. A., Nguyen, T. D., Shingu, Y., Schwarzer, M., Mohr, F. W., Schrepper, A., & Doenst, T. (2010). Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression. The Journal of Thoracic and Cardiovascular Surgery, 140(5), 1160-7. https://doi.org/10.1016/j.jtcvs.2010.08.003
Amorim PA, et al. Myocardial Infarction in Rats Causes Partial Impairment in Insulin Response Associated With Reduced Fatty Acid Oxidation and Mitochondrial Gene Expression. J Thorac Cardiovasc Surg. 2010;140(5):1160-7. PubMed PMID: 20850803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression. AU - Amorim,Paulo A, AU - Nguyen,T Dung, AU - Shingu,Yasushige, AU - Schwarzer,Michael, AU - Mohr,Friedrich W, AU - Schrepper,Andrea, AU - Doenst,Torsten, Y1 - 2010/09/17/ PY - 2010/03/31/received PY - 2010/07/31/revised PY - 2010/08/04/accepted PY - 2010/9/21/entrez PY - 2010/9/21/pubmed PY - 2010/11/9/medline SP - 1160 EP - 7 JF - The Journal of thoracic and cardiovascular surgery JO - J Thorac Cardiovasc Surg VL - 140 IS - 5 N2 - 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. SN - 1097-685X UR - https://www.unboundmedicine.com/medline/citation/20850803/Myocardial_infarction_in_rats_causes_partial_impairment_in_insulin_response_associated_with_reduced_fatty_acid_oxidation_and_mitochondrial_gene_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-5223(10)00869-X DB - PRIME DP - Unbound Medicine ER -