Discovery of a potent GIPR peptide antagonist that is effective in rodent and human systems

ABSTRACT:

Objective

Glucose-dependent insulinotropic polypeptide (GIP) is one of the two major incretin factors that regulate metabolic homeostasis. Genetic ablation of its receptor (GIPR) in mice confers protection against diet-induced obesity (DIO), while GIPR neutralizing antibodies produce additive weight reduction when combined with GLP-1R agonists in preclinical models and clinical trials. Conversely, GIPR agonists have been shown to promote weight loss in rodents, while dual GLP-1R/GIPR agonists have proven superior to GLP-1R monoagonists for weight reduction in clinical trials. We sought to develop a long-acting, specific GIPR peptide antagonist as a tool compound suitable for investigating GIPR pharmacology in both rodent and human systems.

Methods

We report a structure–ac

SUBMITTER: Yang B 

PROVIDER: S-EPMC9719863 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature