mRNA expression analysis

Analysis of leukocytes cell subpopulation in B-hGCGR mice

Analysis of T cell subpopulation in B-hGCGR mice

In vivo efficacy of anti-human GCGR antibody with B-hGCGR mice

In vivo efficacy of anti-human GCGR antibody with B-hGCGR mice

Wild-type C57BL/6 and B-hGCGR mice were treated with crotedumab (in house) or isotype control antibody (n = 6). Blood were collected on Day 11 for triglycerides and cholesterol analysis. Serum levels of TG (A) and TC (B). HDL-C (C) and LDL-C (D) levels in serum. Serum levels of TG was reduced, while TC, HDL-C and LDL-C were increased in the anti-human GCGR antibody treated male mice group compared to the isotype control. All of the results in B-hGCGR mice were similar to those in the wild-type C57BL/6. Results indicated that lipid metabolism in humanized B-hGCGR mice was similar to the wild-type C57BL/6. Results indicated that anti-human GCGR antibody was efficacious in controlling blood lipid in male B-hGCGR mice. Values are expressed as mean ± SEM. TG, triglycerides; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol.  

In vivo efficacy of anti-human GCGR antibody with diet-induced obese (DIO) B-hGCGR mice

Anti-human GCGR antibody reduces blood glucose in DIO B-hGCGR mice. Male B-hGCGR mice were fed with high-fat diet throughout the study. Anti-human GCGR antibody crotedumab (in house) was administered by intraperitoneal injection on day 0 after diet-induced. Body weights, levels of blood glucose and hormones  were measured periodically (n = 10). A. Body weights. B. Random blood glucose from male mice before and at multiple time points after injection of crotedumab (in house) or isotype antibody. C. IPGTT on day 5. D. Area under the curve for the IPGTT shown in C. Serum levels of (E) insulin, (F) glucagon, (G) GLP-1 on Day 14 and Day 28. Anti-GCGR antibody significantly reduced body weight, random blood glucose and IPGTT compared to the isotype control in male DIO B-hGCGR mice. Serum levels of insulin, glucagon and GLP-1 were changed with dose-dependent. Results indicated that anti-human GCGR antibody was efficacious in controlling body weight and blood glucose in B-hGCGR mice. Values are expressed as mean ± SEM. IPGTT, Intraperitoneal glucose tolerance test. 

Single doses of anti-human GCGR antibody treatment increased LDL-C and HDL-C in male DIO B-hGCGR mice. 
Male B-hGCGR mice were fed with high-fat diet throughout the study. Anti-human GCGR antibody crotedumab (in house) was administered by intraperitoneal injection on day 0 after diet-induced for 95 days (n = 10). Blood were collected on Day 28 for detecting the serum levels of TG (A), TC (B), HDL-C (C), LDL-C (D), ALT (E), AST (F). Serum levels of TG, ALT and AST in the three treatment groups were similar to that in the isotype group, while serum levels of HDL-C and LDL-C were significantly increased in the high dose treatment group compared to the isotype control. TC levels were also increased with dose-dependent, although with no significant difference. Values are expressed as mean ± SEM. TG, triglycerides; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol. ALT,  alanine transaminase; AST,  aspartate aminotransferase.

Single doses of anti-human GCGR antibody treatment induced α-cell hyperplasia  in male DIO B-hGCGR mice. 
Male B-hGCGR mice were fed with high-fat diet throughout the study. Anti-human GCGR antibody crotedumab (in house) was administered by intraperitoneal injection on day 0 after diet-induced for 95 days (n = 10). Pancreases were collected on Day 28 for morphometric analysis. (A) Glucagon and insulin immunohistochemistry of representative pancreas sections. α cell area (B) and β cell area (C) measured in (A). (D) Islet number per pancreas section. Results showed that α cell area was increased with dose dependent. Anti-human GCGR antibody had no effect on β cell area or islet number per pancreas area. Values are expressed as mean ± SEM.