Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2025-01-20 DOI:10.1007/s10557-025-07670-9

Xinyu Zhang, Chao Cao, Fei Zheng, Chang Liu, Xiuqing Tian

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引用次数: 0

Abstract

Background: Glucagon-like peptide-1 (GLP-1) is a crucial incretin hormone secreted by intestinal endocrine L cells. Given its pivotal physiological role, researchers have developed GLP-1 receptor agonists (GLP-1 RAs) through structural modifications. These analogues display pharmacological effects similar to those of GLP-1 but with augmented stability and are regarded as an effective means of regulating blood glucose levels in clinical practice.

Objective: This review aims to comprehensively summarize the role of GLP-1 RAs in the management of diabetes mellitus (DM) and cardiovascular disease (CVD), with a particular emphasis on the underlying signal transduction pathways and their therapeutic potential.

Methods: A comprehensive review was carried out through literature research.

Results and discussion: In pancreatic β-cells, GLP-1 RAs regulate the secretion of insulin and glucagon in a glucosedependent manner by influencing signaling pathways such as cAMP, PI3K, and MAPK. They also contribute to the regulation of blood glucose levels by promoting the proliferation of β-cells and inhibiting apoptosis in these cells. Recent comprehensive studies have also demonstrated the favorable impact of GLP-1 RAs on cardiovascular wellbeing. In addition to the cardiovascular protection afforded by glucose metabolism regulation, a large body of evidence from animal and cellular studies has corroborated the beneficial effects of GLP-1 RAs on conditions such as heart failure (HF), hypertension, and ischemic cardiomyopathy. These benefits are mainly attributed to the alleviation of inflammatory responses, reduction of oxidative stress, and prevention of cell apoptosis. Clinical data shows that GLP-1 RAs can reduce the risk of major adverse cardiovascular events (MACE) in diabetic patients.

Conclusion: GLP-1 RAs play an important role in the management of both diabetes and cardiovascular diseases. They show potential therapeutic value through the modulation of multiple signal transduction pathways. However, there may still be some issues in practical applications that require further research and resolution.

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GLP-1受体激动剂在糖尿病和心血管疾病中的治疗潜力：机制和临床意义

背景：胰高血糖素样肽-1 （Glucagon-like peptide-1, GLP-1）是肠道内分泌L细胞分泌的一种重要的肠促胰岛素激素。鉴于其关键的生理作用，研究人员通过结构修饰开发了GLP-1受体激动剂（GLP-1 RAs）。这些类似物的药理作用与GLP-1相似，但稳定性增强，在临床实践中被认为是调节血糖水平的有效手段。目的：本文旨在全面总结GLP-1 RAs在糖尿病（DM）和心血管疾病（CVD）治疗中的作用，特别强调潜在的信号转导途径及其治疗潜力。方法：通过文献研究进行综合综述。结果和讨论：在胰腺β-细胞中，GLP-1 RAs通过影响cAMP、PI3K和MAPK等信号通路，以葡萄糖依赖的方式调节胰岛素和胰高血糖素的分泌。它们还通过促进β-细胞的增殖和抑制这些细胞的凋亡来调节血糖水平。最近的综合研究也证明了GLP-1 RAs对心血管健康的有利影响。除了通过糖代谢调节提供心血管保护外，动物和细胞研究的大量证据证实了GLP-1 RAs对心力衰竭（HF）、高血压和缺血性心肌病等疾病的有益作用。这些好处主要是由于减轻炎症反应，减少氧化应激，防止细胞凋亡。临床资料显示，GLP-1 RAs可降低糖尿病患者发生重大心血管不良事件（MACE）的风险。结论：GLP-1 RAs在糖尿病和心血管疾病的治疗中发挥重要作用。它们通过调节多种信号转导通路显示出潜在的治疗价值。然而，在实际应用中可能还存在一些问题，需要进一步研究和解决。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.