The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets.

ABSTRACT: The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake to facilitate glucose tolerance¹. The GLP-1 receptor (GLP-1R) is an established drug target for the treatment of diabetes and obesity², whereas the therapeutic potential of the GIP receptor (GIPR) is a subject of debate. Tirzepatide is an agonist at both the GIPR and GLP-1R and is a highly effective treatment for type 2 diabetes and obesity^3,4. However, although tirzepatide activates GIPR in cell lines and mouse models, it is not clear whether or how dual agonism contributes to its therapeutic benefit. Islet beta cells express both the GLP-1R and the GIPR, and insulin secretion is an establi

SUBMITTER: El K 

PROVIDER: S-EPMC10290954 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature