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Endocrinol Metab : Endocrinology and Metabolism


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Jong-Ik Hwang  (Hwang JI) 1 Article
Obesity and Metabolism
A Novel Long-Acting Glucagon-Like Peptide-1 Agonist with Improved Efficacy in Insulin Secretion and β-Cell Growth
Hee Young Kim, Jong-Ik Hwang, Mi Jin Moon, Jae Young Seong
Endocrinol Metab. 2014;29(3):320-327.   Published online September 25, 2014
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  • 10 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   

Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by cleavage of proglucagon in intestinal L-cells. In the pancreas, GLP-1 stimulates post-prandial insulin secretion, promotes insulin biosynthesis, and improves insulin sensitivity. Because of its insulinotropic activity, GLP-1 has been considered a good candidate drug for treatment of diabetes mellitus. However, clinical use of GLP-1 has been limited by its short half-life, as a result of rapid degradation by dipeptidyl peptidase-IV (DPP-IV).


We designed a novel GLP-1 analog, Xenopus GLP-1 (xGLP)-E4. The Ala residue in the second position of xGLP was replaced with a Ser residue to increase the half-life in the body. The C-terminal tail of exendin-4 was added to enhance the binding affinity for the GLP-1 receptor (GLP1R). The potency of GLP-1 and its analogs was determined by luciferase assay. The stability of GLP1R agonists was evaluated by determining the activity of agonists that had been preincubated in the presence of fetal bovine serum, which contains innate DPP-IV activity. The effects of xGLP-E4 on insulin secretion and β-cell growth were investigated using insulin enzyme-linked immunosorbent assay and cell counting.


xGLP-E4 exhibited improved stability against DPP-IV activity and increased potency to GLP1R, compared with GLP-1. An increase in glucose-dependent insulin secretion was observed in xGLP-E4-treated pancreatic β-cells. The effect of xGLP-E4 on β-cell growth was greater than that of GLP-1.


We developed a novel GLP-1 analog, xGLP-E4, that shows prolonged longevity and improved efficacy. This analog is a potential candidate for treatment of type 2 diabetes.


Citations to this article as recorded by  
  • Novel GLP-1(28–36) amide-derived hybrid peptide A3 with weight loss and hypoglycemic activities
    Chen Wang, Binbin Gong, Qianqian Zhu, Jing Han, Lidan Sun
    European Journal of Pharmacology.2023; 961: 176200.     CrossRef
  • Intranasal Delivery of a Methyllanthionine-Stabilized Galanin Receptor-2-Selective Agonist Reduces Acute Food Intake
    Anneke Kuipers, Márta Balaskó, Erika Pétervári, Andreas Koller, Susanne M. Brunner, Gert N. Moll, Barbara Kofler
    Neurotherapeutics.2021; 18(4): 2737.     CrossRef
  • Low-Dose Decitabine Assists Human Umbilical Cord-Derived Mesenchymal Stem Cells in ProtectingβCells via the Modulation of the Macrophage Phenotype in Type 2 Diabetic Mice
    Jing Xue, Yu Cheng, Haojie Hao, Jieqing Gao, Yaqi Yin, Songyan Yu, Junyan Zou, Jiejie Liu, Qi Zhang, Yiming Mu
    Stem Cells International.2020; 2020: 1.     CrossRef
  • DR10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus
    W. Wang, X. Wen, W. Duan, X. Wang, Y. Chen, J. Dong, Z. Yang, J. Fang, Z. Zhou, G. Yao, Y. Fang, Y. Huang
    Journal of Endocrinological Investigation.2020; 43(5): 653.     CrossRef
  • Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors
    Michael Furlong, Jae Young Seong
    Biomolecules & Therapeutics.2017; 25(1): 57.     CrossRef
  • Comparison of exenatide and acarbose on intra-abdominal fat content in patients with obesity and type-2 diabetes: A randomized controlled trial
    Li Shi, Jing Zhu, Ping Yang, Xiaoqiang Tang, Wenlong Yu, Changjie Pan, Moyu Shen, Dalong Zhu, Jinluo Cheng, Xinhua Ye
    Obesity Research & Clinical Practice.2017; 11(5): 607.     CrossRef
  • Mesenchymal stem cell therapy in type 2 diabetes mellitus
    Li Zang, Haojie Hao, Jiejie Liu, Yijun Li, Weidong Han, Yiming Mu
    Diabetology & Metabolic Syndrome.2017;[Epub]     CrossRef
  • Exendin-4 Inhibits Hepatic Lipogenesis by Increasing β-Catenin Signaling
    Mi Hae Seo, Jinmi Lee, Seok-Woo Hong, Eun-Jung Rhee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Won-Young Lee, Catherine Mounier
    PLOS ONE.2016; 11(12): e0166913.     CrossRef
  • Development of Spexin-based Human Galanin Receptor Type II-Specific Agonists with Increased Stability in Serum and Anxiolytic Effect in Mice
    Arfaxad Reyes-Alcaraz, Yoo-Na Lee, Gi Hoon Son, Nam Hoon Kim, Dong-Kyu Kim, Seongsik Yun, Dong-Hoon Kim, Jong-Ik Hwang, Jae Young Seong
    Scientific Reports.2016;[Epub]     CrossRef
  • Articles in 'Endocrinology and Metabolism' in 2014
    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
  • Biased signalling: the instinctive skill of the cell in the selection of appropriate signalling pathways
    Ying Liu, Yang Yang, Richard Ward, Su An, Xiao-Xi Guo, Wei Li, Tian-Rui Xu
    Biochemical Journal.2015; 470(2): 155.     CrossRef
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