Toxicological Research

  • 제34권2호
  • /
  • Pages.151-162
  • /
  • 2018
  • /
  • 1976-8257(pISSN)
  • /
  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling

  • Ahn, Mi Young (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Kim, Ban Ji (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Yoon, Hyung Joo (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Hwang, Jae Sam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Park, Kun-Koo (Pharmacogenechips Inc.)
  • 투고 : 2018.02.09
  • 심사 : 2018.03.14
  • 발행 : 2018.04.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

키워드

참고문헌

  1. Yan, W., Zhou, B., Shen, Y. and Xu, G. (2015) Antioxidant and antithrombotic therapies for diabetic kidney disease. Iran. J. Kidney Dis., 9, 413-420.
  2. Lepedda, A.J., Muro, P.D., Capobianco, G. and Formato, M. (2017) Significance of urinary glycosaminoglycans/proteoglycans in the evaluation of type 1 and type 2 diabetes complications. J. Diabetes Complicat., 31, 149-155. https://doi.org/10.1016/j.jdiacomp.2016.10.013
  3. Kubaski, F., Osago, H., Mason, R.W., Yamaguchi, S., Kobayashi, H., Tsuchiya, M., Orii, T. and Tomatsu, S. (2017) Glycosaminoglycans detection methods: application of mass spectrometry. Mol. Genet. Metab., 120, 67-77. https://doi.org/10.1016/j.ymgme.2016.09.005
  4. Li, R., Xing, J., Mu, X., Wang, H., Zhang, L., Zhao, Y. and Zhang, Y. (2015) Sulodexide therapy for the treatment of diabetic nephropathy, a meta-analysis and literature review. Drug Des. Devel. Ther., 9, 6275-6283.
  5. Ahn, M.Y., Kim, B.J., Kim, H.J., Yoon, H.J., Jee, S.D., Hwang, J.S. and Park, K.K. (2017). Anti-obesity effect of Bombus ignitus queen glycosaminoglycans in rats on a highfat diet. Int. J. Mol. Sci., 18, E681. https://doi.org/10.3390/ijms18030681
  6. Ahn, M.Y., Kim, B.J., Kim, H.J., Hwang, J.S., Jung, Y.S. and Park, K.K. (2017) Anti-aging effect and gene expression profiling of dung beetle glycosaminoglycan in aged rats. Biomater. Res., 21, 5. https://doi.org/10.1186/s40824-017-0091-9
  7. Xia, L., Bai, L., Yi, L., Liu, B., Chu, C., Liang, Z., Li, P., Jiang, Z. and Zhao, Z. (2007) Authentication of the 31 species of toxic and potent chinese materia medica (T/PCMM) by microscopic technique, part 1: three kinds of toxic and potent animal CMM. Microsc. Res. Tech., 70, 960-968. https://doi.org/10.1002/jemt.20500
  8. Kim, Y.S., Jo, Y.Y., Chang, I.M., Toida, T., Park, Y. and Linhardt, R.J. (1996) A new glycosaminoglycan from the giant african snail Achatina fulica. J. Biol. Chem. 271, 11750-11755. https://doi.org/10.1074/jbc.271.20.11750
  9. Fratz, E.J., Hunter, G.A. and Ferreira, G.C. (2014) Expression of murine 5-aminolevulinate synthase variants causes protoporphyrin IX accumulation and light-induced mammalian cell death. PLoS ONE, 9, e93078. https://doi.org/10.1371/journal.pone.0093078
  10. Song, J., Liu, H., Ressom, H.W., Tiwari, S. and Ecelbarger, C.M. (2008) Chronic Rosigiltazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray by microarray analysis. Exp. Clin. Endocrinol. Diabetes, 116, 315-325. https://doi.org/10.1055/s-2008-1042429
  11. Wang, F., Wan, A. and Rodrigues, B. (2013) The function of heparanase in diabetes and its complications. Can. J. Diabetes, 37, 332-338. https://doi.org/10.1016/j.jcjd.2013.05.008
  12. Ahn, M.Y., Hwang, J.S., Yoon, H.J. and Yun, E.Y. (2012) Anti-diabetic composition comprising glycosaminoglycans derived insect. Korean patient 10-120419.
  13. Heishi, M., Ichihara, J., Teramoto, R., Itakura, Y., Hayashi, K., Ishikawa, H., Gomi, H., Sakai, J., Kanaoka, M., Taiji, M. and Kimura, T. (2006) Global gene expression analysis in liver of obese diabetic db/db mice treated with metformin. Diabetologia, 49, 1647-1655. https://doi.org/10.1007/s00125-006-0271-y
  14. Dou, J., Ma, J., Liu J., Wang, C., Johnsson, E., Yao, H., Zhao, J. and Pan, C. (2018) Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: results from the START study, a multicenter, randomized, double-blind, active-controlled, phase 3 trial. Diabetes Obes. Metab., 20, 590-598. https://doi.org/10.1111/dom.13117
  15. Mata, M.D.I., Garrido-Maraver, J., Cotan, D., Cordero, M.D., Oropesa-Avila, M., Izquierdo, L.G., Miguel, M.D., Lorite, J.B., Infante, E.R., Ybot, P., Jackson, S. and Sanchez-Alcazar, J.A. (2012) Recovery of MERRF fibroblasts and cybrids pathophysiology by Coenzyme Q10. Neurotherapeutics, 9, 446-463. https://doi.org/10.1007/s13311-012-0103-3
  16. Ishida, H., Yamashita, C., Kuruta, Y., Yoshida, Y. and Noshiro, M. (2000) Insulin is a dominant suppressor of sterol 12a-hydroxylase P450 (CYP8B) expression in rat liver possible role of insulin in Circadian rhythm of CYP8B. J. Biochem., 127, 57-64. https://doi.org/10.1093/oxfordjournals.jbchem.a022584
  17. Kaur, A., Patankar, J.V., de Haan, W., Ruddle, P., Wijesekara, N., Groen, A.K., Verchere, C.B., Singaraja, R.R. and Hayden, M.R. (2015) Loss of cyp8b1 improves glucose homeostasis by increasing GLP-1. Diabetes, 64, 1168-1179. https://doi.org/10.2337/db14-0716
  18. Mortensen, O.H., Nielsen, A.R., Erikstrup, C., Plomgaard, P., Fischer, C.P., Krogh-Madsen, R., Lindegaard, B., Petersen, A.M., Taudorf, S. and Pedersen, B.K. (2009) Calprotectin - a novel marker of obesity. PLoS ONE, 4, e7419. https://doi.org/10.1371/journal.pone.0007419
  19. Kraakman, M.J., Lee, M.K.S., Al-Sharea, A., Dragoljevic, D., Barrett, T.J., Montenont, E., Basu, D., Heywood, S., Kammoun, H.L., Flynn, M., Whillas, A., Hanssen, N.M.J., Febbraio, M.A., Westein, E., Fisher, E.A., Chin-Dusting, J., Cooper, M.E., Berger, J.S., Goldberg, I.J., Nagareddy, P.R. and Murphy, A.J. (2017) Neutrophil-derived S100 calciumbinding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes. J. Clin. Invest., 127, 2133-2147. https://doi.org/10.1172/JCI92450
  20. Giudicelli, V., Chaume, D. and Lefranc, M. (2005) IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res., 33, D256-D261.
  21. Zhou, H. and Rigoutsos, I. (2014) The emerging roles of GPRC5A in diseases. Oncoscience, 1, 765-776. https://doi.org/10.18632/oncoscience.104
  22. Tanaka, T., Kubota, M., Shinohara, K., Yasuda, K. and Kato, J. (2003) In vivo analysis of the cyclin D1 promotor during early embryogenesis in Xenopus. Cell Struct. Funct., 28, 165-177. https://doi.org/10.1247/csf.28.165
  23. Chowdhury, K.H., Montgomery, M.K., Morris, M.J., Cognard, E., Shepherd, R.R. and Smith, G.C. (2015) Glucagon phosphorylate serine 552 of beta-catenin leading to increased expression of cyclinD1 and C-Myc in isolated rat liver. Arch. Physiol. Biochem., 121, 88-96. https://doi.org/10.3109/13813455.2015.1048693
  24. Lauver, D.A. and Lucchesi, B.R. (2006) Sulodexide: a renewed interest in this glycosaminoglycan. Cardiovasc. Drug Rev., 24, 214-226. https://doi.org/10.1111/j.1527-3466.2006.00214.x