Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism.

ABSTRACT:

Objective

Structurally-improved GIP analogs were developed to determine precisely whether GIP receptor (GIPR) agonism or antagonism lowers body weight in obese mice.

Methods

A series of peptide-based GIP analogs, including structurally diverse agonists and a long-acting antagonist, were generated and characterized in vitro using functional assays in cell systems overexpressing human and mouse derived receptors. These analogs were characterized in vivo in DIO mice following acute dosing for effects on glycemic control, and following chronic dosing for effects on body weight and food intake. Pair-feeding studies and indirect calorimetry were used to survey the mechanism for body weight lowering. Congenital Gipr-/- and Glp1r-/- DIO mice were used to investigate the selectivity

SUBMITTER: Mroz PA 

PROVIDER: S-EPMC6358549 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature