AACR 2021: Anti-GCGR in vivo efficacy evaluated in a new humanized hGCGR mouse model

AACR 2021: Anti-GCGR in vivo efficacy evaluated in a new humanized hGCGR mouse model

Author: Rufeng Zhang, Chengzhang Shang, Yuting Hu, Veronika Chromikova, Qingcong Lin

  • 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. 

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