The glucagon receptor (GCGR) is a Class B GPCR that regulates the secretion of glucose from the liver into the bloodstream in response to glucagon. It plays a significant role in the maintenance of glucose homeostasis and is hence regarded as a viable target for the treatment of diabetes, obesity, and hypoglycemia. These disorders are significant contributors to the hazards facing human health. Whereupon, fully comprehending the glucagon receptors carries weight on the drug development of diseases.
Fig.1 Glucagon action in the MBH and the DVC regulates glucose and energy homeostasis.1
Cell-based in vitro assays with high sensitivity and reproducibility features have been a powerful tool for the discovery of structurally diverse compounds that may have therapeutic potential. In order to boost the development of drug discovery, Creative Biolabs incorporates this approach with GPCR functional assay and has successfully developed a Magic™ in vitro cell-based glucagon receptor functional assay service.
In our Magic™ in vitro cell-based glucagon receptor functional assay service, we characterize compounds and their capacity to modify glucagon receptors by examining changes in second messenger concentrations and downstream calcium fluxes caused by receptor activation. Creative Biolabs is dedicated to providing top-ranking services and presenting high-quality outcomes for global customers. Meanwhile, we are capable of helping each customer to:
Fig.2 The activation of glucagon receptors.2
Our Magic™ in vitro cell-based glucagon receptor functional assay service has the capacity to benefit you with:
| Development and characterization of a novel glucagon-like peptide-1 receptor antibody | |
| METHODS: The researchers employed a naïve phage display selection technique to extract single-chain variable fragments (ScFvs) that bind to GLP1R. Glp1R0017, the ScFv with the greatest affinity, was transformed into a human IgG1 and further characterized. To assess antagonistic action in vitro, three methods were utilized: a live cell cAMP imaging test, an insulin secretion assay, and a homogeneous time-resolved fluorescence assay based on cAMP in GLP1R-overexpressing cell lines. | RESULTS: Glp1R0017, a monoclonal antibody to GLP1R, was chosen from naïve antibody phage display libraries. GLP-1R antagonistic activity was limited to cells overexpressing GLP-2 receptors, the glucagon receptor, or the GIPR. Glp1R0017 inhibited GLP-1-stimulated cAMP and insulin production in INS-1 832/3 cells. |
Fig.3 GLP-1 reversed the antagonism of Glp1R0017 to mouse GLP-1R.3
| LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept | |
| METHODS: LY3437943 (LY) was designed to be a strong agonist at the human GCGR, GIPR, and GLP-1R. HEK-293 clonal cell lines expressing either the human GCGR, human GIPR, or human GLP-1R were employed to quantify cAMP buildup as the second messenger downstream of receptor activation to determine the inherent potency of LY. | RESULTS: The cAMP assays revealed that LY is 2.9-fold less powerful than human glucagon at the human GCGR and 8.9-fold more potent than GIP (1-42) NH2 at the human GIPR. LY is 2.5-fold less effective than GLP1(7-36) NH2 at the human GLP-1R. In the functional assays, the data showed that LY is a complete agonist at the GCGR, GIPR, and GLP-1R. |
Fig.4 Celluar cAMP accumulation after LY3437943 agonist stimulated.4
Creative Biolabs, as a frontrunner in the GPCR functional assay field, is committed to offering cutting-edge service and innovative approaches to every customer. If you have any questions concerning our Magic™ in vitro cell-based glucagon receptor functional assay service, feel free to contact us. Everyone here can't wait to get started working with you.
References
For Research Use Only.
