Browse > Article
http://dx.doi.org/10.5483/BMBRep.2013.46.12.106

Novel AGLP-1 albumin fusion protein as a long-lasting agent for type 2 diabetes  

Kim, Yong-Mo (Alteogen Inc.)
Lee, Sang Mee (Alteogen Inc.)
Chung, Hye-Shin (Alteogen Inc.)
Publication Information
BMB Reports / v.46, no.12, 2013 , pp. 606-610 More about this Journal
Abstract
Glucagon like peptide-1 (GLP-1) regulates glucose mediated-insulin secretion, nutrient accumulation, and ${\beta}$-cell growth. Despite the potential therapeutic usage for type 2 diabetes (T2D), GLP-1 has a short half-life in vivo ($t_{1/2}$ <2 min). In an attempt to prolong half-life, GLP-1 fusion proteins were genetically engineered: GLP-1 human serum albumin fusion (GLP-1/HSA), AGLP-1/HSA which has an additional alanine at the N-terminus of GLP-1, and AGLP-1-L/HSA, in which a peptide linker is inserted between AGLP-1 and HSA. Recombinant fusion proteins secreted from the Chinese Hamster Ovary-K1 (CHO-K1) cell line were purified with high purity (>96%). AGLP-1 fusion protein was resistant against the dipeptidyl peptidase-IV (DPP-IV). The fusion proteins activated cAMP-mediated signaling in rat insulinoma INS-1 cells. Furthermore, a C57BL/6N mice pharmacodynamics study exhibited that AGLP-1-L/HSA effectively reduced blood glucose level compared to AGLP-1/HSA.
Keywords
Dipeptidyl peptidase-IV; Fusion protein; Glucagon like peptide-1; Human serum albumin; Type 2 diabetes;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 Baggio, L. L. and Drucker, D. J. (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132, 2131-2157.   DOI   ScienceOn
2 Holst, J. J. (2007) The physiology of glucagon-like peptide 1. Physiol. Rev. 87, 1409-1439.   DOI   ScienceOn
3 Quoyer, J., Longuet, C., Broca, C., Linck, N., Costes, S., Varin, E., Bockaert, J., Bertrand, G. and Dalle, S. (2010) GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a $\beta$-arrestin 1-mediated ERK1/2 activation in pancreatic $\beta$-cells. J. Biol. Chem. 285, 1989-2002.   DOI   ScienceOn
4 Doyle, M. and Egan, J. M. (2007) Mechanisms of action of GLP-1 in the pancreas. Pharmacol. Ther. 113, 546-593.   DOI   ScienceOn
5 Jhala, U. S., Canettieri, G., Screaton, R. A., Kulkarni, R. N., Krajewski, S., Reed, J., Walker, J., Lin, X., White, M. and Montminy, M. (2003) cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev. 17, 1575-1580.   DOI   ScienceOn
6 Kodama, S., Toyonaga, T., Kondo, T., Matsumoto, K., Tsuruzoe, K., Kawashima, J., Goto, H., Kume, K., Kume, S., Sakakida, M. and Araki, E. (2005) Enhanced expression of PDX-1 and Ngn3 by exendin-4 during $\beta$ cell regeneration in STZ-treated mice. Biochem. Biophysic. Res. Comm. 327, 1190-1196.
7 Zhou, J., Chu, J., Wang, Y. H., Wang, H., Zhuang, Y. P. and Zhang, S. L. (2008) Purification and bioactivity of exendin-4, a peptide analogue of GLP-1, expressed in pichia pastoris. Biotechnol. Lett. 30, 651-656.   DOI
8 Gao, Z., Bai, G., Chen, J., Zhang, Q., Pan, P., Bai, F. and Geng, P. (2009) Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in pichia pastoris. Biosci. Biotechnol. Biochem. 73, 688-694.   DOI   ScienceOn
9 Oh, J. Y., Lee, C. W., Jang, S. H., Yoo, S. B. and Chung, H. S. (2009) Novel DPP-IV-resistant analogs of GLP-1: The N-terminal extension of GLP-1 by a single amino acid. Bull. Korean Chem. Soc. 30, 2471-2474.   과학기술학회마을   DOI   ScienceOn
10 Garber, A. J. (2011) Long-acting glucagon-like peptide 1receptor agonists. Diabetes Care 34, S279-S284.   DOI   ScienceOn
11 Liu, B., Dong, Q., Wang, M., Shi, L., Wu, Y., Yu, X., Shi, Y., Shan, Y., Jiang, C., Zhang, X., Gu, T., Chen, Y. and Kong, W. (2010) Preparation, characterization, and pharmacodynamics of exenatide-loaded poly (DL-lactic-co-glycolic acid) microspheres. Chem. Pharm. Bull. 58, 1474-1479.   DOI   ScienceOn
12 Huang, Y. S., Chen, Z., Chen, Y. Q., Ma, G. C., Shan, J. F., Liu, W. and Zhou, L. F. (2008) Preparation and characterization of a novel exendin-4 human serum albumin fusion protein expressed in Pichia pastoris. J. Pept. Sci. 14, 588-595.   DOI   ScienceOn
13 Kim, B. J., Zhou, J., Martin, B., Carlson, O. D., Maudsley, S., Greig, N. H., Mattson, M. P., Ladenheim, E. E., Wustner, J., Turner, A., Sadeghi, H. and Egan, J. M. (2010) Transferrin fusion technology: A novel approach to prolonging biological half-life of insulinotropic peptides. J. Pharm. Exp. Ther. 334, 682-692.   DOI   ScienceOn
14 Yeom, J. A., Kim, S. E., Park, H. S., Ham, D. S., Sun C. L, Kim J. W., Cho, J. H., and Yoon, K. H. (2011) Both sitagliptin analogue & pioglitazone preserve the $\beta$-cell proportion in the islets with different mechanism in non-obese and obese diabetic mice. BMB Rep. 44(11), 713-718.   과학기술학회마을   DOI   ScienceOn
15 Wang Q, Chen, K., Liu, R., Zhao, F., Gupta, S., Zhang, N. and Prud'homme, G. J. (2010) Novel GLP-1 fusion chimera as potent long acting GLP-1 receptor agonist. PLoS One 5, e12734 1-9.
16 Bak, E. J., Park, H. G., Lee, C. H., Lee, T. I., Woo, G. H., Na, Y. W., Yoo, Y. J. and Cha, J. H. (2011) Effects of novel chalcone derivatives on α-glucoside, dipeptidyl peptidase-4, and adipocyte differentiation in vitro. BMB Rep. 44, 410-414.   과학기술학회마을   DOI   ScienceOn
17 Neumiller, J. J. (2009) Differential chemistry (structure), mechanism of action, and pharmacology of GLP-1 receptor agonists and DPP-4 inhibitors. J. American Pharm. Associ. 49, S16-S29.   DOI   ScienceOn
18 Chung, H. S., Oh, J. Y., Yoo, S. B., Lee, S. M. and Cho, H. S. (2011) 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. Regul. Pept. 170, 1-3.   DOI   ScienceOn
19 Son, Y. K., Hong, D. H., Kim, D. J., Firth, A. L., and Park, W. S. (2011) Direct effect of protein kinase C inhibitors on cardiovascular in ion channels. BMB Rep. 44, 559-565.   과학기술학회마을   DOI   ScienceOn
20 Baggio, L. L., Huang, Q., Brown, T. J. and Drucker, D. J. (2004) A recombinant human glucagon-like peptide (GLP)-1-albumin protein (Albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes 53, 2492-2500.   DOI   ScienceOn