The role of G protein-signaling pathways in physiological processes
G protein-coupled receptors (GPCR) comprise the largest family of transmembrane receptors and their signaling pathways are involved in a variety of physiological functions. However, analyzing the effect of a single GPCR in a specific tissue in vivo is nearly impossible because many GPCRs belong to families of related receptors and become activated by similar ligands. The presence of the endogenous agonist and the distribution of the desired receptor in different tissues further complicate the study. To overcome those limitations, receptors with newly designed abilities were developed. These receptors, so-called Designer Receptors Exclusively Activated by Designer Drug (DREADD), do not respond to their endogenous ligand but to otherwise pharmacological inert substances. Using transgenic animal models, DREADDs can help to decipher the impact of a single G protein pathway in specific tissues.
The relevance of Adhesion GPCRs in glucose and energy homeostasis
It is well established that G protein-signaling pathways regulate pancreatic islet and adipocyte function. However, the family of Adhesion GPCR (aGPCR) is not well characterized in this context although expression analysis revealed high frequency for several receptors of this family. Therefore, we are analyzing the contribution of aGPCRs in adipose tissue, pancreatic islet, and hepatocyte function. We are using cell culture and animal models to study the role of receptor activation and knock-down / knock-out on specific metabolic functions.
