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

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.

Keywords: astrocyte; beta cell; blood glucose; exendin; food intake; gliosis; inflammation; liraglutide; macrophage; microglia; neuroprotection; semaglutide.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Astrocytes / metabolism
  • Diabetes Mellitus*
  • Glaucoma*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Obesity

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptide 1