AACR 2021: Anti-GCGR in vivo efficacy evaluated in a new humanized hGCGR mouse model
- Binding of glucagon to its receptor, GCGR, results in an increase in intracellular cAMP levels, which plays a role in promoting glycogenolysis and gluconeogenesis, altogether elevating blood glucose levels.
- Biocytogen generated a humanized B-hGCGR mouse model; human GCGR protein and mRNA expression was confirmed in B-hGCGR mice.
- Anti-human GCGR antibody treatment reduced random blood glucose and fasting blood glucose levels, and improved glucose tolerance.
- Anti-human GCGR antibody treatment blocked the functional response to glucagon in B-hGCGR mice with increased efficiency compared to targeting the wild-type murine receptor using antagonists.
- B-hGCGR mice are a promising model for preclinical in vivo pharmacodynamic assessment of anti-GCGR antibodies.