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胰高血糖素样肽-1 受体:作用机制与治疗进展。

Glucagon-like peptide-1 receptor: mechanisms and advances in therapy.

机构信息

Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.

Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.

出版信息

Signal Transduct Target Ther. 2024 Sep 18;9(1):234. doi: 10.1038/s41392-024-01931-z.

Abstract

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and is found primarily on the surfaces of various cell types within the human body. This receptor specifically interacts with GLP-1, a key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, and several other crucial biological functions. In recent years, GLP-1 medications have become a focal point in the medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, and broad development prospects. This article thoroughly traces the developmental milestones of GLP-1 drugs, from their initial discovery to their clinical application, detailing the evolution of diverse GLP-1 medications along with their distinct pharmacological properties. Additionally, this paper explores the potential applications of GLP-1 receptor agonists (GLP-1RAs) in fields such as neuroprotection, anti-infection measures, the reduction of various types of inflammation, and the enhancement of cardiovascular function. It provides an in-depth assessment of the effectiveness of GLP-1RAs across multiple body systems-including the nervous, cardiovascular, musculoskeletal, and digestive systems. This includes integrating the latest clinical trial data and delving into potential signaling pathways and pharmacological mechanisms. The primary goal of this article is to emphasize the extensive benefits of using GLP-1RAs in treating a broad spectrum of diseases, such as obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, musculoskeletal inflammation, and various forms of cancer. The ongoing development of new indications for GLP-1 drugs offers promising prospects for further expanding therapeutic interventions, showcasing their significant potential in the medical field.

摘要

胰高血糖素样肽-1(GLP-1)受体,又称 GLP-1R,是 G 蛋白偶联受体(GPCR)家族的重要组成部分,主要存在于人体各种细胞表面。该受体特异性地与 GLP-1 相互作用,GLP-1 是一种关键激素,在调节血糖水平、脂质代谢和其他几个重要的生物学功能中起着不可或缺的作用。近年来,GLP-1 类药物因其创新的治疗机制、显著的治疗效果和广阔的发展前景,成为医学界的关注焦点。本文全面追溯了 GLP-1 药物的发展里程碑,从最初的发现到临床应用,详细介绍了不同 GLP-1 药物的演变及其独特的药理学特性。此外,本文还探讨了 GLP-1 受体激动剂(GLP-1RAs)在神经保护、抗感染措施、减少各种炎症和增强心血管功能等领域的潜在应用。深入评估了 GLP-1RAs 在多个身体系统中的有效性,包括神经系统、心血管系统、肌肉骨骼系统和消化系统。这包括整合最新的临床试验数据,并深入探讨潜在的信号通路和药理学机制。本文的主要目的是强调使用 GLP-1RAs 治疗广泛疾病(如肥胖症、心血管疾病、非酒精性脂肪性肝病(NAFLD)、神经退行性疾病、肌肉骨骼炎症和各种癌症)的广泛益处。GLP-1 药物新适应证的不断发展为进一步扩大治疗干预提供了广阔前景,展示了其在医学领域的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf0/11408715/371518b0559b/41392_2024_1931_Fig1_HTML.jpg

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