hGLP1R

Fig 1. Detection of GLP1R and Gapdh expression in lung, heart, brain, stomach, salivary gland, duodenum and samll intestine by RT-PCR.

Fig 2. Analysis of hGLP1R expression by IHC. Pancreata from wild-type and hGLP1R mice (HO) were stained using an antibody specific for human GLP1R, and only the pancreas from hGLP1R mice (HO) showed hGLP1R positive signal in pancreatic islet.

Fig 3. Assessment of biochemical parameters in HO hGLP1R mice after high-fat diet feeding. (A) Oral glucose tolerance test (OGTT) in hGLP1R mice after 3 months high-fat diet feeding (n = 5/group); (B) Blood biochemical analysis in hGLP1R mice after 6 months high-fat diet feeding (n = 5/group).

Fig 4. Validation of the hypoglycemic efficacy of the test compound in humanized GLP-1R mice. The oral glucose tolerance test (OGTT) was performed (n=5), and the test compound showed a better hypoglycemic efficacy (p<0.001). The above data indicated that the GLP-1R humanized mouse is an effective model for diabetes drug screening.

Fig 5. Efficacy study of PF06882961 in hGLP1R mice. PF06882961 has shown significant effect in hGLP1R mice in OGTT study, but no effect in C57BL/6 mice.

Fig 6. Efficacy study of PF06882961 in HFD/STZ induced type II diabetes model in hGLPIR mice. PF06882961 could significant decreases the body weight(A); PF06882961 could significantly decrease fast blood glucose level and AUC in OGTT study (B).

Fig 7. Detection of human GLP-1R expression in HO hGLP-1R knockin mice by IHC. Pancreas, salivary gland, colon, heart, lung, brian, stomach and duodenum were collected from homozygous hGLP-1R mice (HO/HO), and analyzed by IHC with anti-human GLP-1R antibody. Human GLP-1R is specifically expressed in islets of the pancreas. Abbr. HO/HO, homozygous.

Table1. Blood routine test results of Hom hGLP-1R mice (Data are presented as mean and ± SEM).

Table2. Biochemistry examinations results of Hom hGLP-1R mice (Data are presented as mean and ± SEM).