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- Title
Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1) analog fusion protein, on CHO recombinant cells and BKS-db mice.
- Authors
Ji, Wan-Wan; Yu, Dong-An; Fan, Min; You, Meng; Lu, You; Li, Er-Bing; Xie, Ning; Yan, Shou-Sheng
- Abstract
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.
- Subjects
GLUCAGON-like peptides; CHIMERIC proteins; TYPE 2 diabetes; HYPOGLYCEMIC agents; SERUM albumin
- Publication
Acta Diabetologica, 2017, Vol 54, Issue 7, p685
- ISSN
0940-5429
- Publication type
Article
- DOI
10.1007/s00592-017-0992-z