The molecular pharmacology of glucagon agonists in diabetes and obesity.
Biased agonism
Diabetes
Dual-agonists
Glucagon
Obesity
Pharmacology
Tri-agonists
Journal
Peptides
ISSN: 1873-5169
Titre abrégé: Peptides
Pays: United States
ID NLM: 8008690
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
05
02
2023
revised:
20
03
2023
accepted:
21
03
2023
medline:
31
5
2023
pubmed:
31
3
2023
entrez:
30
3
2023
Statut:
ppublish
Résumé
Within recent decades glucagon receptor (GcgR) agonism has drawn attention as a therapeutic tool for the treatment of type 2 diabetes and obesity. In both mice and humans, glucagon administration enhances energy expenditure and suppresses food intake suggesting a promising metabolic utility. Therefore synthetic optimization of glucagon-based pharmacology to further resolve the physiological and cellular underpinnings mediating these effects has advanced. Chemical modifications to the glucagon sequence have allowed for greater peptide solubility, stability, circulating half-life, and understanding of the structure-function potential behind partial and "super"-agonists. The knowledge gained from such modifications has provided a basis for the development of long-acting glucagon analogues, chimeric unimolecular dual- and tri-agonists, and novel strategies for nuclear hormone targeting into glucagon receptor-expressing tissues. In this review, we summarize the developments leading toward the current advanced state of glucagon-based pharmacology, while highlighting the associated biological and therapeutic effects in the context of diabetes and obesity.
Identifiants
pubmed: 36997003
pii: S0196-9781(23)00065-7
doi: 10.1016/j.peptides.2023.171003
pmc: PMC10265134
pii:
doi:
Substances chimiques
Glucagon
9007-92-5
Glucagon-Like Peptide 1
89750-14-1
Receptors, Glucagon
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
171003Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
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