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Effects of liraglutide on ANP secretion and cardiac dynamics

To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4(−/−) mice were also established in...

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Autores principales: Luo, Shenghe, Zuo, Yunhui, Cui, Xiaotian, Zhang, Meiping, Jin, Honghua, Hong, Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563649/
https://www.ncbi.nlm.nih.gov/pubmed/37681442
http://dx.doi.org/10.1530/EC-23-0176
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author Luo, Shenghe
Zuo, Yunhui
Cui, Xiaotian
Zhang, Meiping
Jin, Honghua
Hong, Lan
author_facet Luo, Shenghe
Zuo, Yunhui
Cui, Xiaotian
Zhang, Meiping
Jin, Honghua
Hong, Lan
author_sort Luo, Shenghe
collection PubMed
description To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4(−/−) mice were also established in vivo. ANP levels were determined by radioimmunoassay; GLP-1 content was determined by Elisa. The expression levels of GLP-1 receptor (GLP-1R), PI3K/AKT/mTOR, piezo 1, and cathepsin K were analyzed by Western blot. In the clinical study, patients with acute coronary syndrome (ACS) had low levels of plasma GLP-1 but relatively high levels of plasma ANP. In ex vivo (3.2 nmol/L) and in vivo (30 μg/kg) models, liraglutide significantly decreased ANP levels and atrial pulse pressure. Exendin9–39 alone (GLP-1R antagonist) reversibly significantly increased ANP secretion, and the reduction effect of liraglutide on the secretion of ANP was significantly alleviated by Exendin9–39. Exendin9–39 demonstrated slightly decreased atrial pulse pressure; however, combined liraglutide and Exendin9–39 significantly decreased atrial pulse pressure. Ly294002 (PI3K/AKT inhibitor) inhibited the increase of ANP secretion by liraglutide for a short time, while Ly294002 didn't counteract the decrease in pulse pressure by liraglutide in atrial dynamics studies. Liraglutide increased the expression of GLP-1R and PI3K/AKT/mTOR in isolated rat atria and the hearts of mice in vivo, whereas Exendin9–39 reversibly reduced the expression of GLP-1R and PI3K/AKT/mTOR. Piezo 1 was significantly decreased in wild type and DPP-4(−/−) mouse heart or isolated rat atria after being treated with liraglutide. Cathepsin K expression was only decreased in in vivo model hearts. Liraglutide can inhibit ANP secretion while decreasing atrial pulse pressure mediated by GLP-1R. Liraglutide probably plays a role in the reduction of ANP secretion via the PI3K/AKT/mTOR signaling pathway. Piezo 1 and cathepsin K may be involved in the liraglutide mechanism of reduction.
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spelling pubmed-105636492023-10-11 Effects of liraglutide on ANP secretion and cardiac dynamics Luo, Shenghe Zuo, Yunhui Cui, Xiaotian Zhang, Meiping Jin, Honghua Hong, Lan Endocr Connect Research To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4(−/−) mice were also established in vivo. ANP levels were determined by radioimmunoassay; GLP-1 content was determined by Elisa. The expression levels of GLP-1 receptor (GLP-1R), PI3K/AKT/mTOR, piezo 1, and cathepsin K were analyzed by Western blot. In the clinical study, patients with acute coronary syndrome (ACS) had low levels of plasma GLP-1 but relatively high levels of plasma ANP. In ex vivo (3.2 nmol/L) and in vivo (30 μg/kg) models, liraglutide significantly decreased ANP levels and atrial pulse pressure. Exendin9–39 alone (GLP-1R antagonist) reversibly significantly increased ANP secretion, and the reduction effect of liraglutide on the secretion of ANP was significantly alleviated by Exendin9–39. Exendin9–39 demonstrated slightly decreased atrial pulse pressure; however, combined liraglutide and Exendin9–39 significantly decreased atrial pulse pressure. Ly294002 (PI3K/AKT inhibitor) inhibited the increase of ANP secretion by liraglutide for a short time, while Ly294002 didn't counteract the decrease in pulse pressure by liraglutide in atrial dynamics studies. Liraglutide increased the expression of GLP-1R and PI3K/AKT/mTOR in isolated rat atria and the hearts of mice in vivo, whereas Exendin9–39 reversibly reduced the expression of GLP-1R and PI3K/AKT/mTOR. Piezo 1 was significantly decreased in wild type and DPP-4(−/−) mouse heart or isolated rat atria after being treated with liraglutide. Cathepsin K expression was only decreased in in vivo model hearts. Liraglutide can inhibit ANP secretion while decreasing atrial pulse pressure mediated by GLP-1R. Liraglutide probably plays a role in the reduction of ANP secretion via the PI3K/AKT/mTOR signaling pathway. Piezo 1 and cathepsin K may be involved in the liraglutide mechanism of reduction. Bioscientifica Ltd 2023-09-06 /pmc/articles/PMC10563649/ /pubmed/37681442 http://dx.doi.org/10.1530/EC-23-0176 Text en © the author(s) https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Research
Luo, Shenghe
Zuo, Yunhui
Cui, Xiaotian
Zhang, Meiping
Jin, Honghua
Hong, Lan
Effects of liraglutide on ANP secretion and cardiac dynamics
title Effects of liraglutide on ANP secretion and cardiac dynamics
title_full Effects of liraglutide on ANP secretion and cardiac dynamics
title_fullStr Effects of liraglutide on ANP secretion and cardiac dynamics
title_full_unstemmed Effects of liraglutide on ANP secretion and cardiac dynamics
title_short Effects of liraglutide on ANP secretion and cardiac dynamics
title_sort effects of liraglutide on anp secretion and cardiac dynamics
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563649/
https://www.ncbi.nlm.nih.gov/pubmed/37681442
http://dx.doi.org/10.1530/EC-23-0176
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