Biochemical pharmacology

Drug effects of single, double, and triple peptide activators on GIP and GLP-1 hormone receptors

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated

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.

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Funding

Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
PubMed

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