The N-terminal alanine-extended GLP-1/IgG-Fc fusion protein confers resistance to DPP-IV and reduces serum glucose level in db/db mice

被引：12

作者：

Chung, Hye-Shin ^{[1
,2
]}

Oh, Ji-Yeon

Yoo, Seung-Bum ^{[2
]}

Lee, Sang Mee ^{[2
]}

Cho, Heung-Soo ^{[2
]}

机构：

[1] Hannam Univ, Dept Biotechnol, Biochem Lab, Taejon 305811, South Korea

[2] Alteogen Inc, Taejon 305812, South Korea

来源：

REGULATORY PEPTIDES | 2011年 / 170卷 / 1-3期

关键词：

Glucagon-like peptide 1 (GLP-1); IgG-Fc fusion; Dipeptidyl peptidase IV (DPPIV); Type; 2; diabetes; GLUCAGON-LIKE PEPTIDE-1; ANTIHYPERGLYCEMIC ACTIVITY; IN-VIVO; ANALOGS; GLP-1;

D O I：

10.1016/j.regpep.2011.05.002

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The aim of this study was to develop novel long-acting glucagon-like peptide 1 (GLP-1) analogs resistant to dipeptidyl peptidase-IV (DPP-IV). We constructed three fusion proteins comprising GLP-1 and the human immunoglobulin gamma heavy chain (IgG-Fc); wild-type GLP-1 and IgG-Fc (GLP-1/IgG-Fc) and two N-terminal-extended fusion proteins in which an additional Ala (A) or Gly (G) was located on the N-terminus of GLP-1 (A-GLP-1/IgG-Fc or G-GLP-1/IgG-Fc). The fusion proteins expressed in CHO-K1 cells were secreted into medium and purified by Protein A affinity chromatography. Here, we show that the Ala or Gly-extended GLP-1/IgG-Fc fusion protein is resistant to DPP-IV and has increased half-life in vivo. To our surprise, the A-GLP-1/IgG-Fc fusion protein was more effective than wildtype GLP-1/IgG-Fc fusion protein in reducing blood glucose levels in db/db mice. Our findings suggest that the A-GLP-1/IgG-Fc fusion protein could be a potential long-acting GLP-1 receptor agonist for the treatment of insulin-resistant type 2 diabetes. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：1 / 3

页数：3