Reagents and models for detecting endogenous GLP1R and GIPR

Glucagon-like peptide-1 receptor (GLP1R) agonists target the GLP1R, whereas dual GLP1R/ gastric inhibitory polypeptide receptor (GIPR) agonists target both the GLP1R and GIPR. Despite the importance of these drug classes for the treatment of diabetes and obesity, still very little is known about the localization of GLP1R and GIPR themselves. Complicating matters is the low abundance of GLP1R and GIPR mRNA/protein, as well as a lack of specific and validated reagents for their detection. Without knowing where GLP1R and GIPR are located, it is difficult to propose mechanisms of action in the various target organs, and whether this is indirect or direct. In the current review, we will explain the steps needed to properly validate reagents for endogenous GLP1R/GIPR detection, describe the available approaches to visualize GLP1R/GIPR, and provide an update on the state-of-art. The overall aim is to provide a reference resource for researchers interested in GLP1R and GIPR signaling.