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GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy
BACKGROUND: Glucagon-like peptide-1 (GLP-1) reduces cardiovascular events in diabetic patients; however, its counter-protective effects have also been suggested in patients with heart failure and the clear explanation for its mechanisms have not yet been offered. METHODS: The effects of GLP-1 analog...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881987/ https://www.ncbi.nlm.nih.gov/pubmed/31779634 http://dx.doi.org/10.1186/s12933-019-0966-2 |
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author | Shiraki, Aya Oyama, Jun-ichi Nishikido, Toshiyuki Node, Koichi |
author_facet | Shiraki, Aya Oyama, Jun-ichi Nishikido, Toshiyuki Node, Koichi |
author_sort | Shiraki, Aya |
collection | PubMed |
description | BACKGROUND: Glucagon-like peptide-1 (GLP-1) reduces cardiovascular events in diabetic patients; however, its counter-protective effects have also been suggested in patients with heart failure and the clear explanation for its mechanisms have not yet been offered. METHODS: The effects of GLP-1 analog on cardiac function and energy metabolism, especially glycemic and lipid metabolisms were elucidated using non-diabetic J2N-k hamsters which showed spontaneous dilated cardiomyopathy. J2N-k hamsters were treated with PBS (HF group), low-dose (HF-L group) or high-dose liraglutide (HF-H group). RESULTS: In failing heart, GLP-1 analog exerted further deteriorated cardiac function (e.g. positive and negative dP/dt; p = 0.01 and p = 0.002, respectively) with overt fibrosis and cardiac enlargement (heart/body weight, 5.7 ± 0.2 in HF group versus 7.6 ± 0.2 in HF-H group; p = 0.02). The protein expression of cardiac muscles indicated the energy starvation status. Indirect calorimetry showed that failing hearts consumed higher energy and carbohydrate than normal hearts; moreover, this tendency was augmented by GLP-1 analog administration. Upon 10% glucose solution loading with GLP-1 analog administration (HF-H-G group) as complementary experiments, the cardiac function and fibrosis significantly ameliorated, whereas carbohydrate utilization augmented further and lipid utilization reduced more. The prognosis of HF-H-G group also significantly improved (p = 0.025). CONCLUSIONS: Glucagon-like peptide-1 analog caused the relative but desperate shortage of glycemic energy source for the failing cardiac muscles and it may restrict ATP synthesis, resulting in cardiac function deterioration. Therefore, appropriate energy supply and amount of carbohydrate intake should be carefully considered when administrating incretin-related drugs to patients with heart failure. |
format | Online Article Text |
id | pubmed-6881987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68819872019-12-03 GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy Shiraki, Aya Oyama, Jun-ichi Nishikido, Toshiyuki Node, Koichi Cardiovasc Diabetol Original Investigation BACKGROUND: Glucagon-like peptide-1 (GLP-1) reduces cardiovascular events in diabetic patients; however, its counter-protective effects have also been suggested in patients with heart failure and the clear explanation for its mechanisms have not yet been offered. METHODS: The effects of GLP-1 analog on cardiac function and energy metabolism, especially glycemic and lipid metabolisms were elucidated using non-diabetic J2N-k hamsters which showed spontaneous dilated cardiomyopathy. J2N-k hamsters were treated with PBS (HF group), low-dose (HF-L group) or high-dose liraglutide (HF-H group). RESULTS: In failing heart, GLP-1 analog exerted further deteriorated cardiac function (e.g. positive and negative dP/dt; p = 0.01 and p = 0.002, respectively) with overt fibrosis and cardiac enlargement (heart/body weight, 5.7 ± 0.2 in HF group versus 7.6 ± 0.2 in HF-H group; p = 0.02). The protein expression of cardiac muscles indicated the energy starvation status. Indirect calorimetry showed that failing hearts consumed higher energy and carbohydrate than normal hearts; moreover, this tendency was augmented by GLP-1 analog administration. Upon 10% glucose solution loading with GLP-1 analog administration (HF-H-G group) as complementary experiments, the cardiac function and fibrosis significantly ameliorated, whereas carbohydrate utilization augmented further and lipid utilization reduced more. The prognosis of HF-H-G group also significantly improved (p = 0.025). CONCLUSIONS: Glucagon-like peptide-1 analog caused the relative but desperate shortage of glycemic energy source for the failing cardiac muscles and it may restrict ATP synthesis, resulting in cardiac function deterioration. Therefore, appropriate energy supply and amount of carbohydrate intake should be carefully considered when administrating incretin-related drugs to patients with heart failure. BioMed Central 2019-11-28 /pmc/articles/PMC6881987/ /pubmed/31779634 http://dx.doi.org/10.1186/s12933-019-0966-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Investigation Shiraki, Aya Oyama, Jun-ichi Nishikido, Toshiyuki Node, Koichi GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
title | GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
title_full | GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
title_fullStr | GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
title_full_unstemmed | GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
title_short | GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
title_sort | glp-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881987/ https://www.ncbi.nlm.nih.gov/pubmed/31779634 http://dx.doi.org/10.1186/s12933-019-0966-2 |
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