Effects of liraglutide on ANP secretion and cardiac dynamics

Shenghe Luo; Yunhui Zuo; Xiaotian Cui; Meiping Zhang; Honghua Jin; Lan Hong

doi:10.1530/EC-23-0176

Endocrine Connections (Oct 2023)

Effects of liraglutide on ANP secretion and cardiac dynamics

Shenghe Luo,
Yunhui Zuo,
Xiaotian Cui,
Meiping Zhang,
Honghua Jin,
Lan Hong

Affiliations

Shenghe Luo: College of Pharmacy, Yanbian University, Yanji, China
Yunhui Zuo: Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China; Department of Clinical Laboratory, Inner Mongolia Forestry General Hospital (The Second Clinical Medical School of Inner Mongolia University for Nationalities), Yakeshi, China
Xiaotian Cui: Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China
Meiping Zhang: Department of Cardiology, Yanbian University Hospital, Yanji, China
Honghua Jin: Department of Pharmacy, Yanbian University Hospital, Yanji, China
Lan Hong: Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China

DOI: https://doi.org/10.1530/EC-23-0176
Journal volume & issue: Vol. 12, no. 11
pp. 1 – 11

Abstract

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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 secret ion 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.

Published in Endocrine Connections

ISSN: 2049-3614 (Online)
Publisher: Bioscientifica
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: http://www.endocrineconnections.com/

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