Full text is available at the source.
Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors
Drug effects of single, double, and triple peptide activators on GIP and GLP-1 hormone receptors
AI simplified
Abstract
GIP receptor mono-agonists show biased signaling towards ERK1/2 phosphorylation compared to cAMP accumulation.
- GIP-dependent insulinotropic peptide signaling plays roles in various physiological processes including fat storage and bone health.
- Selective ligands for the GIP receptor have not yet been developed for treating diseases.
- Dual and triple agonists targeting GIPR, GLP-1R, and glucagon receptors are under clinical investigation for improved efficacy in diabetes management.
- The GIPR mono-agonists Pro3GIP and Lys3GIP exhibit preferential signaling towards ERK1/2 activation over cAMP production.
- The triple agonist at GLP-1R, GCGR, and GIPR favors ERK1/2 activation relative to β-arrestin2 recruitment.
- The dual GIPR/GLP-1R agonist LY3298176 also demonstrates biased signaling towards ERK1/2 activation compared to cAMP at both receptors.
AI simplified