Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice.

ABSTRACT:

Objective

Pharmacological strategies that engage multiple mechanisms-of-action have demonstrated synergistic benefits for metabolic disease in preclinical models. One approach, concurrent activation of the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (Gcg) receptors (i.e. triagonism), combines the anorectic and insulinotropic activities of GLP-1 and GIP with the energy expenditure effect of glucagon. While the efficacy of triagonism in preclinical models is known, the relative contribution of GcgR activation remains unassessed. This work aims to addresses that central question.

Methods

Herein, we detail the design of unimolecular peptide triagonists with an empirically optimized receptor potency ratio. These optimized peptide

SUBMITTER: Knerr PJ 

PROVIDER: S-EPMC9305623 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature