GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin secretion via GLP-1 receptor and Gαq signalling pathway in mice.

ABSTRACT:

Aims/hypothesis

Unimolecular peptides targeting the receptors for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) have been shown to improve glycaemic management in both mice and humans. Yet the identity of the downstream signalling events mediated by these peptides remain to be elucidated. Here, we aimed to assess the mechanisms by which a validated peptide triagonist for GLP-1/GIP/GCG receptors (IUB447) stimulates insulin secretion in murine pancreatic islets.

Methods

Islets were isolated from wild-type (WT), Gipr-knockout (Gipr^-/-), Gcgr-knockout (Gcgr^-/-), Glp-1r (also known as Glp1r)/Gipr double-knockout and Trpm5-knockout (Trpm5^-/-) mice, followed by assessment of beta cell function

SUBMITTER: Schreier PCF 

PROVIDER: S-EPMC12534261 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature