The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of G protein-coupled receptors. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1.In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.
The full coding sequence of the human GLP1R gene was inserted into mouse Glp1r gene in B-hGLP1R mice.
mRNA and protein expression analysis
RT-PCR and western blot analysis of GLP1R. The mRNA of human GLP1R was detectable in the lung of the homozygous B-hGLP1R mice, but not detectable in wildtype mice. and we proved that the protein could be expressed normally by western blot analysis. Human and mouse cross-reactive antibodies were used to detect the GLP1R of the wildtype and humanized GLP1R mice.
Protein expression analysis
IHC for human GLP1R expression. Pancreata from wild-type (+/+) and B-hGLP1R mice (H/H) mice were stained using an antibody specific for human GLP1R. and only the pancreas from B-hGLP1R mice (H/H) mice showed hGLP1R positive signal in plasma membrane.