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Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture
The increasing global prevalence of diabetes has been accompanied by a rise in diabetes-related conditions. This includes diabetic cardiomyopathy (DbCM), a progressive form of heart disease that occurs with both insulin-dependent (type-1) and insulin-independent (type-2) diabetes and arises in the a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555155/ https://www.ncbi.nlm.nih.gov/pubmed/31214041 http://dx.doi.org/10.3389/fphys.2019.00639 |
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author | Sowton, Alice P. Griffin, Julian L. Murray, Andrew J. |
author_facet | Sowton, Alice P. Griffin, Julian L. Murray, Andrew J. |
author_sort | Sowton, Alice P. |
collection | PubMed |
description | The increasing global prevalence of diabetes has been accompanied by a rise in diabetes-related conditions. This includes diabetic cardiomyopathy (DbCM), a progressive form of heart disease that occurs with both insulin-dependent (type-1) and insulin-independent (type-2) diabetes and arises in the absence of hypertension or coronary artery disease. Over time, DbCM can develop into overt heart failure. Like other forms of cardiomyopathy, DbCM is accompanied by alterations in metabolism which could lead to further progression of the pathology, with metabolic derangement postulated to precede functional changes in the diabetic heart. Moreover in the case of type-2 diabetes, underlying insulin resistance is likely to prevent the canonical substrate switch of the failing heart away from fatty acid oxidation toward increased use of glycolysis. Analytical chemistry techniques, collectively known as metabolomics, are useful tools for investigating the condition. In this article, we provide a comprehensive review of those studies that have employed metabolomic techniques, namely chromatography, mass spectrometry and nuclear magnetic resonance spectroscopy, to profile metabolic remodeling in the diabetic heart of human patients and animal models. These studies collectively demonstrate that glycolysis and glucose oxidation are suppressed in the diabetic myocardium and highlight a complex picture regarding lipid metabolism. The diabetic heart typically shows an increased reliance on fatty acid oxidation, yet triacylglycerols and other lipids accumulate in the diabetic myocardium indicating probable lipotoxicity. The application of lipidomic techniques to the diabetic heart has identified specific lipid species that become enriched and which may in turn act as plasma-borne biomarkers for the condition. Metabolomics is proving to be a powerful approach, allowing a much richer analysis of the metabolic alterations that occur in the diabetic heart. Careful physiological interpretation of metabolomic results will now be key in order to establish which aspects of the metabolic derangement are causal to the progression of DbCM and might form the basis for novel therapeutic intervention. |
format | Online Article Text |
id | pubmed-6555155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65551552019-06-18 Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture Sowton, Alice P. Griffin, Julian L. Murray, Andrew J. Front Physiol Physiology The increasing global prevalence of diabetes has been accompanied by a rise in diabetes-related conditions. This includes diabetic cardiomyopathy (DbCM), a progressive form of heart disease that occurs with both insulin-dependent (type-1) and insulin-independent (type-2) diabetes and arises in the absence of hypertension or coronary artery disease. Over time, DbCM can develop into overt heart failure. Like other forms of cardiomyopathy, DbCM is accompanied by alterations in metabolism which could lead to further progression of the pathology, with metabolic derangement postulated to precede functional changes in the diabetic heart. Moreover in the case of type-2 diabetes, underlying insulin resistance is likely to prevent the canonical substrate switch of the failing heart away from fatty acid oxidation toward increased use of glycolysis. Analytical chemistry techniques, collectively known as metabolomics, are useful tools for investigating the condition. In this article, we provide a comprehensive review of those studies that have employed metabolomic techniques, namely chromatography, mass spectrometry and nuclear magnetic resonance spectroscopy, to profile metabolic remodeling in the diabetic heart of human patients and animal models. These studies collectively demonstrate that glycolysis and glucose oxidation are suppressed in the diabetic myocardium and highlight a complex picture regarding lipid metabolism. The diabetic heart typically shows an increased reliance on fatty acid oxidation, yet triacylglycerols and other lipids accumulate in the diabetic myocardium indicating probable lipotoxicity. The application of lipidomic techniques to the diabetic heart has identified specific lipid species that become enriched and which may in turn act as plasma-borne biomarkers for the condition. Metabolomics is proving to be a powerful approach, allowing a much richer analysis of the metabolic alterations that occur in the diabetic heart. Careful physiological interpretation of metabolomic results will now be key in order to establish which aspects of the metabolic derangement are causal to the progression of DbCM and might form the basis for novel therapeutic intervention. Frontiers Media S.A. 2019-05-31 /pmc/articles/PMC6555155/ /pubmed/31214041 http://dx.doi.org/10.3389/fphys.2019.00639 Text en Copyright © 2019 Sowton, Griffin and Murray. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Sowton, Alice P. Griffin, Julian L. Murray, Andrew J. Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture |
title | Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture |
title_full | Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture |
title_fullStr | Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture |
title_full_unstemmed | Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture |
title_short | Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture |
title_sort | metabolic profiling of the diabetic heart: toward a richer picture |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555155/ https://www.ncbi.nlm.nih.gov/pubmed/31214041 http://dx.doi.org/10.3389/fphys.2019.00639 |
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