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- W3191008263 abstract "Abstract 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 Exendin-4-Fc, a 66-kDa fusion protein by linking an IgG2 Fc to Exendin-4. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Exendin-4-Fc stimulated insulin secretion in INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The plasma half-life of Exendin-4-Fc in cynomolgus monkeys was approximately 133.92 ± 25.1 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of Exendin-4-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 Exendin-4-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with Exendin-4-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of Exendin-4-Fc demonstrated that it could be a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes." @default.
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- W3191008263 date "2021-08-11" @default.
- W3191008263 modified "2023-09-26" @default.
- W3191008263 title "Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Like Agonist, Exendin-4-Fc" @default.
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- W3191008263 doi "https://doi.org/10.1007/s10989-021-10269-x" @default.
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