Novel Small Molecule Glucagon-Like Peptide-1 Receptor Agonist S6 Stimulates Insulin Secretion From Rat Islets.
glucagon-like peptide-1 receptor (GLP-1R)
insulin secretion
intracellular calcium concentration [(Ca2+)i]
virtual screening
voltage-dependent K+ (Kv) channel
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
06
02
2021
accepted:
12
04
2021
entrez:
17
5
2021
pubmed:
18
5
2021
medline:
18
5
2021
Statut:
epublish
Résumé
Glucagon-like peptide-1 receptor (GLP-1R) agonist-based therapeutics for type 2 diabetes mellitus have attracted worldwide attention. However, there are challenges in the development of small molecule GLP-1R agonists owing to the complexity of ligand recognition and signal induction mechanisms. Here, we attained S6 using virtual screening and fluorescent imaging plate reader (FLIPR)-based calcium assays. The purpose of this study was to identify and characterize S6, a novel small molecule GLP-1R agonist. Data from cellular thermal shift assay (CETSA) and Bio-Layer Interferometry (BLI) indicated that S6 could bind potently with GLP-1R. Radioimmunoassay data showed that S6 potentiated insulin secretion in a glucose-dependent manner and the insulinotropic effect was mediated by GLP-1R. Calcium imaging techniques suggested that S6 elevated the intracellular calcium concentration [(Ca
Identifiants
pubmed: 33995091
doi: 10.3389/fphar.2021.664802
pii: 664802
pmc: PMC8116734
doi:
Types de publication
Journal Article
Langues
eng
Pagination
664802Informations de copyright
Copyright © 2021 Yang, Zhang, Lu, Zhi, Xue, Liu, Liu, Cui, Liu, He, Liu and Zhang.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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