AACR 2022: Developing a Translational Tool for GLP-1-Based Therapeutic Agonists in Humanized GLP1R Mice
- mRNA and protein expression analysis: Human GLP1R mRNA was exclusively detected in the lung of homozygous B-hGLP1R mice compared to wild-type mice by RT-PCR. Similarly, human GLP1R protein was detected by western blot analysis in B-hGLP1R mice.
- Analysis of leukocyte subpopulations: Introduction of human GLP1R in place of its mouse counterpart does not change the overall development, differentiation or distribution of immune cell types in the spleen and blood.
- Functional analysis: Dulaglutide reduced non-fasting blood glucose and fasting blood glucose compared to the PBS in B-hGLP1R mice.
- In vivo efficacy in obese mice: Dulaglutide reduced non-fasting blood glucose, fasting blood glucose, glucagon and food intake in B-hGLP1R obese mice, and increased plasma insulin and GLP-1 secretion, altogether improving glucose tolerance. Similar IPGTT results were observed after treatment with PF-06882961.
Related mouse model: B-hGLP1R mice