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胶质细胞在胰高血糖素样肽-1 的生理学和药理学中的作用:对肥胖、糖尿病、神经退行性变和青光眼的影响。

The role of glia in the physiology and pharmacology of glucagon-like peptide-1: implications for obesity, diabetes, neurodegeneration and glaucoma.

机构信息

Scheie Eye Institute, Philadelphia, Pennsylvania, USA.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

出版信息

Br J Pharmacol. 2022 Feb;179(4):715-726. doi: 10.1111/bph.15683. Epub 2021 Nov 23.

Abstract

The medical applications of glucagon-like peptide-1 receptor (GLP-1R) agonists is evergrowing in scope, highlighting the urgent need for a comprehensive understanding of the mechanisms through which GLP-1R activation impacts physiology and behaviour. A new area of research aims to elucidate the role GLP-1R signalling in glia, which play a role in regulating energy balance, glycemic control, neuroinflammation and oxidative stress. Once controversial, existing evidence now suggests that subsets of glia (e.g. microglia, tanycytes and astrocytes) and infiltrating macrophages express GLP-1Rs. In this review, we discuss the implications of these findings, with particular focus on the effectiveness of both clinically available and novel GLP-1R agonists for treating metabolic and neurodegenerative diseases, enhancing cognition and combating substance abuse. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.

摘要

胰高血糖素样肽-1 受体 (GLP-1R) 激动剂在医学上的应用范围不断扩大,这突显了人们迫切需要全面了解 GLP-1R 激活对生理和行为的影响机制。一个新的研究领域旨在阐明 GLP-1R 信号在神经胶质中的作用,神经胶质在调节能量平衡、血糖控制、神经炎症和氧化应激方面发挥作用。虽然曾经存在争议,但现有证据表明,神经胶质的某些亚群(如小神经胶质细胞、室管膜细胞和星形胶质细胞)和浸润的巨噬细胞表达 GLP-1R。在这篇综述中,我们讨论了这些发现的意义,特别关注临床可用和新型 GLP-1R 激动剂在治疗代谢和神经退行性疾病、增强认知和对抗物质滥用方面的有效性。相关文章:本文是 GLP1 受体配体专题(BJP 75 周年纪念)的一部分。要查看本节中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.

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