Past and present of beta arrestins: A new perspective on insulin secretion and effect.
Biased agonism
Substrate metabolism
β arrestin 1
β arrestin 2
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
05 Oct 2023
05 Oct 2023
Historique:
received:
31
05
2023
revised:
24
07
2023
accepted:
01
08
2023
medline:
31
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
Beta arrestins had been known as intracellular adaptors that uncouple and inactivate the G protein-coupled receptors that they interact with. Their roles as signal initiators for some receptors have recently been recognized. In this review, we focused on their role in mediating metabolic modulation primarily in relation to insulin signaling. Commenced by the upstream receptor, they seem to act like intracellular hubs that divert the metabolic profile of the cell. The amount of metabolic substrates in circulation and their usage/deposition by tissues are controlled by the contribution of all systems in the organism. This control is enabled by the release of hormones such as insulin, glucagon and glucagon-like peptide-1. Intriguingly, some ligands -either agonists or antagonists-of different classes of receptors have preferential properties mediated by β arrestins. This is not surprizing considering that substrate supply and usage should parallel physiological function such as hormone release or muscle contraction. Available data indicate that β arrestins conduct the regulatory role in insulin secretion and action. They may be good candidates to target when the upstream signal demands the function that may compromise the cell. An example is carvedilol that is protective by preventing the stimulatory effects of excessive catecholamines, stimulates mitochondrial function and has preferential clinical outcomes in metabolic disorders.
Sections du résumé
BACKGROUND
BACKGROUND
Beta arrestins had been known as intracellular adaptors that uncouple and inactivate the G protein-coupled receptors that they interact with. Their roles as signal initiators for some receptors have recently been recognized.
SCOPE OF REVIEW
METHODS
In this review, we focused on their role in mediating metabolic modulation primarily in relation to insulin signaling. Commenced by the upstream receptor, they seem to act like intracellular hubs that divert the metabolic profile of the cell. The amount of metabolic substrates in circulation and their usage/deposition by tissues are controlled by the contribution of all systems in the organism. This control is enabled by the release of hormones such as insulin, glucagon and glucagon-like peptide-1. Intriguingly, some ligands -either agonists or antagonists-of different classes of receptors have preferential properties mediated by β arrestins. This is not surprizing considering that substrate supply and usage should parallel physiological function such as hormone release or muscle contraction.
MAJOR CONCLUSIONS
CONCLUSIONS
Available data indicate that β arrestins conduct the regulatory role in insulin secretion and action. They may be good candidates to target when the upstream signal demands the function that may compromise the cell. An example is carvedilol that is protective by preventing the stimulatory effects of excessive catecholamines, stimulates mitochondrial function and has preferential clinical outcomes in metabolic disorders.
Identifiants
pubmed: 37541367
pii: S0014-2999(23)00464-8
doi: 10.1016/j.ejphar.2023.175952
pii:
doi:
Substances chimiques
beta-Arrestins
0
Arrestins
0
Insulin
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
175952Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.