Long-lasting anti-diabetic efficacy of PEGylated FGF-21 and liraglutide in treatment of type 2 diabetic mice

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• 作者：Xianlong Ye ; Jianying Qi ; Guiping Ren ; Pengfei Xu ; Yunzhou Wu ; Shenglong Zhu…
• 关键词：FGF ; 21 ; Liraglutide ; PEGylation ; Diabetes ; Hypoglycemic effect
• 刊名：Endocrine
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：49
• 期：3
• 页码：683-692
• 全文大小：1,081 KB
• 参考文献：1.W. Chen, R.L. Hoo, M. Konishi, N. Itoh, P.C. Lee, H.Y. Ye et al., Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. J. Biol. Chem. 286, 34559-4566 (2011)PubMed Central PubMed View Article
  2.A. Kharitonenkov, T.L. Shiyanova, A. Koester, A.M. Ford, R. Micanovic, E.J. Galbreath et al., FGF-21 as a novel metabolic regulator. J. Clin. Inves. 115, 1627-635 (2005)View Article
  3.W. Wente, A.M. Efanov, M. Brenner, A. Kharitonenkov, A. K?ster, G.E. Sandusky et al., Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes 55, 2470-478 (2006)PubMed View Article
  4.X. Huang, C. Yu, C. Jin, C. Yang, R. Xie, D. Cao et al., Forced expression of hepatocyte-specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis. Mol. Carcinog. 45, 934-42 (2006)PubMed View Article
  5.T. Coskun, H.A. Bina, M.A. Schneider, J.D. Dunbar, C.C. Hu, Y. Chen et al., FGF21 corrects obesity in mice. Endocrinology 149, 6018-127 (2008)PubMed View Article
  6.J. Xu, D.J. Lloyd, C. Hale, S. Stanislaus, M. Chen, G. Sivits et al., FGF21 reverses hepatic steatosis, increases energy expenditure and improves insulin sensitivity in diet-induced obese mice. Diabetes 58, 250-59 (2009)PubMed Central PubMed View Article
  7.A. Kharitonenkov, V.J. Wroblewski, A. Koester, Y.F. Chen, C.K. Clutinger, X.T. Tigno et al., The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148, 774-81 (2007)PubMed View Article
  8.R. Hecht, Y.S. Li, J. Sun, E. Belouski, M. Hall, T. Hager et al., Rationale-based engineering of a potent long-acting FGF21 analog for the treatment of type 2 diabetes. PLoS ONE 7, e49345 (2012)PubMed Central PubMed View Article
  9.B.K. Lee, J.S. Kwon, H.J. Kim, S. Yamamoto, E.K. Lee, Solid-phase PEGylation of recombinant interferon alpha-2a for site-specific modification: process performance, characterization, and in vitro bioactivity. Bioconjug. Chem. 18, 1728-734 (2007)PubMed View Article
  10.Y. Mukai, Y. Yoshioka, Y. Tsutsumi, Phage display and PEGylation of therapeutic proteins. Comb. Chem. High Throughput Screen 8, 145-52 (2005)PubMed View Article
  11.F.M. Veronese, G. Pasut, PEGylation, successful approach to drug delivery. Drug Discov. Today 10, 1451-458 (2005)PubMed View Article
  12.A. Abuchowski, J.R. McCoy, N.C. Palczuk, T. van Es, F.F. Davis, Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J. Biol. Chem. 252, 3582-586 (1977)PubMed
  13.Q. An, Y. Lei, N. Jia, X. Zhang, Y. Bai, J. Yi et al., Effect of site-directed PEGylation of trichosanthin on its biological activity, immunogenicity, and pharmacokinetics. Biomol. Eng. 24, 643-49 (2007)PubMed View Article
  14.X. Ye, J. Qi, G. Sun, G. Ren, S. Zhu, Y. Wu et al., Enhancement of the pharmacological efficacy of FGF-21 by genetic modification and PEGylation. Curr. Pharm. Biotechnol. 14, 1287-298 (2013)PubMed View Article
  15.Z. Huang, H. Wang, M. Lu, C. Sun, X. Wu, Y. Tan et al., A better anti-diabetic recombinant human fibroblast growth factor 21 (rhFGF21) modified with polyethylene glycol. PLoS ONE 6, e20669 (2011)PubMed Central PubMed View Article
  16.B. Zinman, J. Gerich, J.B. Buse, A. Lewin, S. Schwartz, P. Raskin et al., Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met?+?TZD). Diabet. Care 32, 1224-230 (2009)View Article
  17.D. Russell-Jones, A. Vaag, O. Schmitz, B.K. Sethi, N. Lalic, S. Antic et al., Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met?+?SU): a randomised controlled trial. Diabetologia 52, 2046-055 (2009)PubMed Central PubMed View Article
  18.M. Marre, J. Shaw, M. Br?ndle, W.M. Bebakar, N.A. Kamaruddin, J. Strand et al., Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26?weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet. Med. 26, 268-78 (2009)PubMed Central PubMed View Article
  19.M. Nauck, A. Frid, K. Hermansen, N.S. Shah, T. Tankova, I.H. Mitha et al., Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabet. Care 32, 84-0 (2009)View Article
  20.J.B. Buse, J. Rosenstock, G. Sesti, W.E. Schmidt, E. Montanya, J.H. Brett et al., Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LE
• 作者单位：Xianlong Ye (1)
  Jianying Qi (1)
  Guiping Ren (1)
  Pengfei Xu (1)
  Yunzhou Wu (1)
  Shenglong Zhu (2)
  Dan Yu (1)
  Shujie Li (1)
  Qiang Wu (1)
  Rasool Lubna Muhi (1) (3)
  Deshan Li (1) (4)
  
  1. Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, No. 59 Mucai Street Xiangfang District, Harbin, 150030, Heilongjiang, People’s Republic of China
  2. School of Food Science and Technology, Jiangnan University, State Key Laboratory of Food Science and Technology, Wuxi, People’s Republic of China
  3. University of Baghdad, Baghdad, Iraq
  4. Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, People’s Republic of China
  
• 刊物主题：Endocrinology; Diabetes; Internal Medicine; Science, general;
• 出版者：Springer US
• ISSN：1559-0100

文摘

Fibroblast growth factor-21 (FGF-21) is a new member of the FGF family and potential drug candidate for the treatment of type 2 diabetes mellitus. However, FGF-21 protein has short half-life in vivo, which severely affects its clinical application. In the present study, PEGylated FGF-21 was prepared by modifying the N-terminus of hFGF-21 with 20?kDa mPEG-ALD. The long-acting hypoglycemic effect of PEGylated FGF-21 and liraglutide was compared on type 2 diabetic db/db mice. The pharmacological efficacy of the compounds was evaluated by blood glucose levels, body weight, glycosylated hemoglobin levels, insulin levels, oral glucose tolerance test, lipid levels, and liver function parameters. We noticed that both PEGylated FGF-21 and liraglutide could significantly decrease plasma glucose in db/db mice. However, comparing to liraglutide treatments, PEGylated FGF-21 therapy resulted in more significant effect in lowering blood glucose levels and glycosylated hemoglobin levels, alleviating insulin resistance, improving lipid profile, liver function, and glucose control of the experimental mice. Our results suggest that PEGylated FGF-21 appears more beneficial anti-diabetic effect in type 2 diabetic mice than liraglutide, which holds significant promise as an ideal candidate for the treatment of type 2 diabetic patients.