التفاصيل البيبلوغرافية
| العنوان: |
Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Agonist, GLP-1-IgG2σ-Fc. |
| المؤلفون: |
Yang, Yi1,2, Chen, Fang2, Wan, Deyou2, Liu, Yunhui2, Yang, Li2, Feng, Hongru2, Cui, Xinling2, Gao, Xin2 gaox_amms@126.com, Song, Haifeng1,2 |
| المصدر: |
PLoS ONE. 5/27/2016, Vol. 11 Issue 5, p1-14. 14p. |
| مصطلحات موضوعية: |
*GLUCAGON-like peptide-1 receptor, *GENE expression, *GLYCEMIC control, *CHIMERIC proteins, *CD26 antigen, *WESTERN immunoblotting |
| مستخلص: |
Human GLP-1 (glucagon-like peptide-1) can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered GLP-1-IgG2σ-Fc, a 68-kDa fusion protein linking a variant human GLP-1 (A8G/G26E/R36G) to a human IgG2σ constant heavy-chain. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Western blotting showed that the expressed protein was immunoreactive to both GLP-1 and IgG antibodies. GLP-1-IgG2σ-Fc stimulated insulin secretion from INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The half-life of GLP-1-IgG2σ-Fc in cynomolgus monkeys was approximately 57.1 ± 4.5 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of GLP-1-IgG2σ-Fc (1 mg/kg) reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that GLP-1-IgG2σ-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with GLP-1-IgG2σ-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of GLP-1-IgG2σ-Fc demonstrated that it represented a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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