Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1) analog fusion protein, on CHO recombinant cells and BKS-db mice.
AIMS
GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice.


METHODS
To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro. In vivo, body weight, food intake, non-fasting and fasting blood glucose, oral glucose tolerance test, blood glucose and insulin levels, liver histology, liver function parameters and antibody levels in BKS-db mice were investigated to evaluate the effects of GW002. Albiglutide was chosen as a positive comparator.


RESULTS
Cyclic adenosine monophosphate levels were increased in a dose-dependent manner in cells. In vivo studies demonstrated that GW002 lowers non-fasting and fasting blood glucose levels and improves glucose tolerance and insulin secretion in BKS-db mice. The degree of hepatic steatosis and hepatic biochemical indexes was also decreased. In this study, the mice body weight was not reduced significantly.


CONCLUSIONS
The above results showed that the efficacy of GW002 in BKS-db mice displayed a significant hypoglycemic effect, which indicated that GW002 might be a potential candidate for the treatment of T2DM.
['Ji|Wan-Wan|WW|', 'Yu|Dong-An|DA|', 'Fan|Min|M|', 'You|Meng|M|', 'Lu|You|Y|', 'Li|Er-Bing|EB|', 'Xie|Ning|N|', 'Yan|Shou-Sheng|SS|']
D000818:Animals D001786:Blood Glucose D001835:Body Weight D016466:CHO Cells D006224:Cricetinae D003412:Cricetulus D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D052216:Glucagon-Like Peptide 1 D000067757:Glucagon-Like Peptide-1 Receptor D005951:Glucose Tolerance Test D006801:Humans D007004:Hypoglycemic Agents D007328:Insulin D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic
GW002 GLP-1 Diabetes Hypoglycemic effect GLP-1/HSA fusion protein