# GLP-1 and GIP receptor signaling in beta cells – A review of receptor interactions and co-stimulation

Review · Ashok Mayendraraj, METTE MARIE ROSENKILDE, Lærke S. Gasbjerg

- Archive id: doi:10.1016/j.peptides.2022.170749
- Published: 2022-01-19
- Venue: Peptides
- DOI: https://doi.org/10.1016/j.peptides.2022.170749
- PMID: 35065096
- Citations: 158
- Source URL: https://doi.org/10.1016/j.peptides.2022.170749
- PDF: https://www.sciencedirect.com/science/article/pii/S0196978122000158/pdf
- Provenance: openalex+europepmc

## Abstract

Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are two class B1 G protein-coupled receptors, which are stimulated by the gastrointestinal hormones GLP-1 and GIP, respectively. In the pancreatic beta cells, activation of both receptors lead to increased cyclic adenosine monophosphate (cAMP) and glucose-dependent insulin secretion. Marketed GLP-1R agonists such as dulaglutide, liraglutide, exenatide and semaglutide constitute an expanding drug class with beneficial effects for persons suffering from type 2 diabetes and/or obesity. In recent years another drug class, the GLP-1R-GIPR co-agonists, has emerged. Especially the peptide-based, co-agonist tirzepatide is a promising candidate for a better treatment of type 2 diabetes by improving glycemic control and weight reduction. The mechanism of action for tirzepatide include biased signaling of the GLP-1R as well as potent GIPR signaling. Since the implications of co-targeting these closely related receptors concomitantly are challenging to study in vivo, the pharmacodynamic mechanisms and downstream signaling pathways of the GLP-1R-GIPR co-agonists in general, are not fully elucidated. In this review, we present the individual signaling pathways for GLP-1R and GIPR in the pancreatic beta cell with a focus on the shared signaling pathways of the two receptors and interpret the implications of GLP-1R-GIPR co-activation in the light of recent co-activating therapeutic compounds.

_Abstract reproduced under CC-BY (publisher license, via OpenAlex)._

Topics: [GLP-1 & Incretin Therapies](https://space-kitty.com/topics/glp1-metabolic)

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