Skip to main content
Log in

Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice

  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of β-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired β-cell function in high glucose condition. By the screening of various natural products blocking β-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent thein vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced β-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-κB activation. Here, to verify thein vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ.Ex vivo analysis of β-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Rererences

  • Ahmad, F., Khalid, P., Khan, M. M., Rastogi, A. K., and Kidwai, J. R., Insulin like activity in (-) epicatechin.Acta Diabetol. Lat., 26, 291–300 (1989).

    Article  PubMed  CAS  Google Scholar 

  • An, N. H., Han, M. K., Um, C., Park, B. H., Park, B. J., Kim, H. K., and Kim, U. H., Significance of ecto-cyclase activity of CD38 in insulin secretion of mouse pancreatic islet cells.Biochem. Biophys. Res. Commun., 282, 781–786 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Broadhurst, C. L., Polansky, M. M., and Anderson, R. A., Insulin-like biological activity of culinary and medicinal plant aqueous extractsin vitro.J. Agric. Food Chem., 48, 849–852 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Han, M. K., Epigallocatechin gallate, a constituent of green tea, suppresses (Ed- confirm versus original title) cytokine-induced pancreatic β-cell damage.Exp. Mol. Med., 35, 136–139 (2003).

    PubMed  CAS  Google Scholar 

  • Kao, Y. H., Hiipakka, R. A., and Liao, S., Modulation of endocrine systems and food intake by green tea epigallocatechin gallate.Endocrinology, 141, 980–987 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Katiyar, S. K. and Mukhtar, H., Tea antioxidants in cancer chemoprevention.J. Cell. Biochem. Suppl., 27, 59–67 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Kolb-Bachofen, V., Epstein, S., Kiesel, U., and Kolb, H., Low-dose streptozocin-induced diabetes in mice. Electron microscopy reveals single-cell insulitis before diabetes onset.Diabetes, 37, 21–27 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Kumar, P., Delfino, V., McShane, P., Gray, D. W., and Morris, P. J., Rapid assessment of islet cell viability by MTT assay after cold storage in different solutions.Transplant. Proc., 26, 814 (1994).

    PubMed  CAS  Google Scholar 

  • Like, A. A. and Rossini, A. A., Streptozotocin-induced pancreatic insulitis: a (Ed- confirm) new model of diabetes mellitus.Science, 193, 415–417 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Lukic, M. L., Stosic-Grujicic, S., and Shahin, A., Effector mechanisms in low-dose streptozotocin-induced diabetes.Dev. Immunol., 6, 119–128 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Maedler, K., Sergeev, P., Ris, F., Oberholzer, J., Joller-Jemelka, H. I., Spinas, G. A., Kaiser, N., Halban, P. A., and Donath, M. Y., Glucose-induced beta cell production of IL-1β contributes to glucotoxicity in human pancreatic islets.J. Clin. Invest., 110, 851–860 (2002).

    PubMed  CAS  Google Scholar 

  • Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti, M., Hillaire-Buys, D., Novelli, M., and Ribes, G., Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide.Diabetes, 47, 224–229 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Mensah-Brown, E. P., Stosic Grujicic, S., Maksimovic, D., Jasima, A., Shahin, A., and Lukic, M. L., Downregulation of apoptosis in the target tissue prevents low-dose streptozotocin-induced autoimmune diabetes.Mol. Immunol., 38, 941–946 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Nakayama, M., Suzuki, K., Toda, M., Okubo, S., Hara, Y., and Shimamura, T., Inhibition of the infectivity of influenza virus by tea polyphenols.Antiviral Res., 21, 289–299 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Rabinovitch, A. and Suarez-Pinzon, W. L., Cytokines and their roles in pancreatic islet β-cell destruction and insulin-dependent diabetes mellitus.Biochem. Pharmacol., 55, 1139–1149 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Ryu, J. K., Kim, D. J., Lee, T., Kang, Y. S., Yoon, S. M., and Suh, J. K., The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats.Yonsei Med. J., 44, 236–241 (2003).

    PubMed  CAS  Google Scholar 

  • Stosic-Grujicic, S., Maksimovic, D., Badovinac, V., Samardzic, T., Trajkovic, V., Lukic, M., and Mostarica Stojkovic, M., Antidiabetogenic effect of pentoxifylline is associated with systemic and target tissue modulation of cytokines and nitric oxide production.J. Autoimmun., 16, 47–58 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Tannous, M., Amin, R., Popoff, M. R., Fiorentini, C., and Kowluru, A., Positive modulation by Ras of interleukin-1β-mediated nitric oxide generation in insulin-secreting clonal β (HIT-T15) cells.Biochem. Pharmacol., 62, 1459–1468 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, K., Taminato, T., Usami, M., Ishida, H., Kitano, N., Fukumoto, H., Koh, G., Kurose, T., Yamada, Y., and Yano, H., Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model.Metabolism, 37, 1040–1044 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Yang, C. S. and Wang, Z. Y., Tea and cancer.J. Nat. Cancer Inst., 85, 1038–1049 (1993).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Myung -Kwan Han.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, E.K., Hur, H. & Han, M.K. Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice. Arch Pharm Res 26, 559–563 (2003). https://doi.org/10.1007/BF02976881

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02976881

Key words

Navigation