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Streptozotocin-resistant BRIN-BD11 cells possess wide spectrum of toxin tolerance and enhanced insulin-secretory capacity

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Abstract

Since streptozotocin (STZ) exhibits beta-cell toxicity, mediated through diverse mechanisms, multiple toxin resistance can be expected in insulin-secretory cells rendered STZ-resistant. RINm5F, but not all cell lines surviving STZ treatment, possess higher insulin content than native parental cells and additional tolerance against alloxan. To understand the impact of STZ tolerant cell selection on toxin resistance and insulin-secretory function, STZ-resistant BRIN-BD11 cells were generated by iterative acute exposure to 20 mM STZ. These cells, denoted BRINst cells, exhibited resistance to toxic challenges from STZ, H2O2, and ninhydrin. Insulin content and both glucose and arginine-stimulated insulin secretion were significantly enhanced in BRINst cells. The toxin-resistance of BRINst cells was gradually lost during continuous cultivation without STZ challenge. However, enhanced insulin secretory capacity at high passage in BRINst cells persisted. Although total SOD activity was decreased, catalase activity was increased and appeared to be important for the ninhydrin and STZ resistance of BRINst cells. This was associated with reductions of both STZ- and ninhydrin-induced DNA damage, although DNA repair was abolished. Further characterization of cells exhibiting multiple toxin tolerance and an enhanced insulin secretory function could provide useful lessons for understanding of beta-cell survival.

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References

  1. J.W. Baynes, in: Drugs, Diet, and Disease, ed by P.R. Flatt, C. Ioannides, (Ellis Horwood Limited, 1995)

  2. P.R. Flatt, O. Shibier, C. Ioannides, S.K. Swanston Flatt, Exp. Clin. Endocrinol. 93, 193–202 (1989)

    Article  PubMed  CAS  Google Scholar 

  3. C.C. Rerup, Pharmacol. Rev. 22, 485–518 (1970)

    PubMed  CAS  Google Scholar 

  4. P. Bouchard, P. Sai, G. Reach, I. Caubarrere, D. Ganeval, R. Assan, Diabetes 31, 40–45 (1982)

    Article  PubMed  CAS  Google Scholar 

  5. T. Helgason, M.R. Jonasson, Lancet 2, 716–720 (1981)

    Article  PubMed  CAS  Google Scholar 

  6. J.H. Karam, P.A. Lewitt, C.W. Young, R.E. Nowlain, B.J. Frankel, H. Fujiya, Z.R. Freedman, G.M. Grodsky, Diabetes 29, 971–978 (1980)

    Article  PubMed  CAS  Google Scholar 

  7. C.J. Bailey, P.R. Flatt, in: Textbook of Diabetes, ed. by J.C. Pickup, G. Williams (Blackwell Science, Osney Mead, 2003)

  8. F. Lally, A.J. Bone, in Textbook of Diabetes, ed. by J.C. Pickup, G. Williams (Blackwell Science, Osney Mead, 2003)

  9. M. Elsner, B. Guldbakke, M. Tiedge, R. Munday, S. Lenzen, Diabetologia 43, 1528–1533 (2000)

    Article  PubMed  CAS  Google Scholar 

  10. W.J. Schnedl, S. Ferber, J.H. Johnson, C.B. Newgard, Diabetes 43, 1326–1333 (1994)

    Article  PubMed  CAS  Google Scholar 

  11. B.E. Tuch, S. Beynon, M.T. Tabiin, R. Sassoon, R.J. Goodman, A.M. Simpson, J Autoimmun. 10, 239–244 (1997)

    Article  PubMed  CAS  Google Scholar 

  12. C. Park, J.R. Kim, J.K. Shim, B.S. Kang, Y.G. Park, K.S. Nam, Y.C. Lee, C.H. Kim, Arch. Biochem. Biophys. 362, 217–224 (1999)

    Article  PubMed  CAS  Google Scholar 

  13. K. Asayama, D. English, A.E. Slonim, I.M. Burr, Diabetes 33, 160–163 (1984)

    Article  PubMed  CAS  Google Scholar 

  14. K.S. Saini, C. Thompson, C.M. Winterford, N.I. Walker, D.P. Cameron, Biochem. Mol. Biol. Int. 39, 1229–1236 (1996)

    PubMed  CAS  Google Scholar 

  15. N. Takasu, I. Komiya, T. Asawa, Y. Nagasawa, T. Yamada, Diabetes 40, 1141–1145 (1991)

    Article  PubMed  CAS  Google Scholar 

  16. J. Turk, J.A. Corbett, S. Ramanadham, A. Bohrer, M.L. McDaniel, Biochem. Biophys. Res. Commun. 197, 1458–1464 (1993)

    Article  PubMed  CAS  Google Scholar 

  17. D.M. Kokkinakis, M.A. von Wronski, T.H. Vuong, T.P. Brent, S.C. Schold Jr., Br. J. Cancer 75, 779–788 (1997)

    PubMed  CAS  Google Scholar 

  18. M. Murata, A. Takahashi, I. Saito, S. Kawanishi, Biochem. Pharmacol. 57, 881–887 (1999)

    Article  PubMed  CAS  Google Scholar 

  19. N.A. Berger, Radiat. Res. 101, 4–15 (1985)

    Article  PubMed  CAS  Google Scholar 

  20. H. Okamoto, Biomed. Biochim. Acta. 44, 15–20 (1985)

    PubMed  CAS  Google Scholar 

  21. A. Bast, G. Wolf, R. Oberbaumer, R. Walther, Diabetologia 45, 867–876 (2002)

    Article  PubMed  CAS  Google Scholar 

  22. H. Chen, E.C. Carlson, L. Pellet, J.T. Moritz, P.N. Epstein, Diabetes 50, 2040–2046 (2001)

    Article  PubMed  CAS  Google Scholar 

  23. K.D. Kroncke, K. Fehsel, A. Sommer, M.L. Rodriguez, V. Kolb-Bachofen, Biol. Chem. Hoppe. Seyler. 376, 179–185 (1995)

    PubMed  CAS  Google Scholar 

  24. K. Bloch, P. Vardi, Int. J. Exp. Diabetes Res. 1, 233–237 (2001)

    Article  Google Scholar 

  25. K.O. Bloch, M. Vorobeychik, K. Yavrians, P. Vardi, Biochem. Pharmacol. 65, 1797–1805 (2003)

    PubMed  CAS  Google Scholar 

  26. K.O. Bloch, R. Zemel, O.V. Bloch, H. Grief, P. Vardi, Int. J. Exp. Diabetes Res. 1, 211–219 (2000)

    Article  PubMed  CAS  Google Scholar 

  27. G. Chen, H.E. Hohmeier, R. Gasa, V.V. Tran, C.B. Newgard, Diabetes 49, 562–570 (2000)

    Article  PubMed  CAS  Google Scholar 

  28. G. Chen, H.E. Hohmeier, C.B. Newgard, J. Biol. Chem. 276, 766–772 (2001)

    Article  PubMed  CAS  Google Scholar 

  29. K. Bloch, P. Vardi, Diabetes Metab. Res. Rev. 21, 253–261 (2005)

    Article  PubMed  CAS  Google Scholar 

  30. Y. Abdel-Wahab, H.-K. Liu, N.H. McClenaghan, P.R. Flatt, Diabetic Med. 23, 33–34 (2006)

    Google Scholar 

  31. N.H. McClenaghan, C.R. Barnett, E. Ah-Sing, Y.H. Abdel-Wahab, F.P. O’Harte, T.W. Yoon, S.K. Swanston-Flatt, P.R. Flatt, Diabetes 45, 1132–1140 (1996)

    Article  PubMed  CAS  Google Scholar 

  32. N.H. McClenaghan, C.R. Barnett, F.P. O’Harte, P.R. Flatt, J Endocrinol. 151, 349–357 (1996)

    Article  PubMed  CAS  Google Scholar 

  33. V.J. McKelvey-Martin, M.H. Green, P. Schmezer, B.L. Pool-Zobel, M.P. De Meo, A. Collins, Mutat. Res. 288, 47–63 (1993)

    PubMed  CAS  Google Scholar 

  34. P.R. Flatt, C.J. Bailey, Diabetologia 20, 573–577 (1981)

    Article  PubMed  CAS  Google Scholar 

  35. K. Grankvist, J. Sehlin, I.B. Taljedal, Acta Pharmacol. Toxicol. (Copenh.) 58, 175–181 (1986)

    CAS  Google Scholar 

  36. H. Kaneto, J. Fujii, H.G. Seo, K. Suzuki, T. Matsuoka, M. Nakamura, H. Tatsumi, Y. Yamasaki, T. Kamada, N. Taniguchi, Diabetes 44, 733–738 (1995)

    Article  PubMed  CAS  Google Scholar 

  37. E. Strandell, S. Sandler, J. Endocrinol. 153, 81–86 (1997)

    Article  PubMed  CAS  Google Scholar 

  38. S.P. LeDoux, S.E. Woodley, N.J. Patton, G.L. Wilson, Diabetes 35, 866–872 (1986)

    Article  PubMed  CAS  Google Scholar 

  39. Z. Ling, M. Van de Casteele, D.L. Eizirik, D.G. Pipeleers, Diabetes 49, 340–345 (2000)

    Article  PubMed  CAS  Google Scholar 

  40. I. Flechner, K. Maruta, V. Burkart, K. Kawai, H. Kolb, U. Kiesel, Diabetes Res. 13, 67–73 (1990)

    PubMed  CAS  Google Scholar 

  41. N.S. Kwon, S.H. Lee, C.S. Choi, T. Kho, H.S. Lee, Faseb J. 8, 529–533 (1994)

    PubMed  CAS  Google Scholar 

  42. P.R. Flatt, S.K. Swanston Flatt, K.S. Tan, V. Marks, Gen. Pharmacol. 18, 293–297 (1987)

    PubMed  CAS  Google Scholar 

  43. S. Lortz, M. Tiedge, T. Nachtwey, A.E. Karlsen, J. Nerup, S. Lenzen, Diabetes 49, 1123–1130 (2000)

    Article  PubMed  CAS  Google Scholar 

  44. M. Tiedge, H. Steffeck, M. Elsner, S. Lenzen, Diabetes 48, 514–523 (1999)

    Article  PubMed  CAS  Google Scholar 

  45. N. Takasu, T. Asawa, I. Komiya, Y. Nagasawa, T. Yamada, J. Biol. Chem. 266, 2112–2114 (1991)

    PubMed  CAS  Google Scholar 

  46. T. Ishii, H. Iwahashi, R. Sugata, R. Kido, J. Biochem. (Tokyo) 104, 610–615 (1988)

    CAS  Google Scholar 

  47. M. Poje, B. Rocic, M. Sikirica, I. Vickovic, M. Bruvo, J. Med. Chem. 26, 861–864 (1983)

    Article  PubMed  CAS  Google Scholar 

  48. C.A. Delaney, D.L. Eizirik, Braz. J. Med. Biol. Res. 29, 569–579 (1996)

    PubMed  CAS  Google Scholar 

  49. Y. Uchigata, H. Yamamoto, A. Kawamura, H. Okamoto, J. Biol. Chem. 257, 6084–6088 (1982)

    PubMed  CAS  Google Scholar 

Download references

Acknowlegments

This work was mainly supported by University Research Strategy Funding and Vice Chancellor’s research studentship award to H-K Liu and partially supported by a research grant from NRICM (NRICM94-DHM-6).

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Authors and Affiliations

  1. School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK

    Hui-Kang Liu, Jane T. McCluskey, Neville H. McClenghan & Peter R. Flatt

  2. Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei, 112, Taiwan

    Hui-Kang Liu

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  1. Hui-Kang Liu
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  2. Jane T. McCluskey
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  4. Peter R. Flatt
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Correspondence to Hui-Kang Liu.

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Liu, HK., McCluskey, J.T., McClenghan, N.H. et al. Streptozotocin-resistant BRIN-BD11 cells possess wide spectrum of toxin tolerance and enhanced insulin-secretory capacity. Endocr 32, 20–29 (2007). https://doi.org/10.1007/s12020-007-9000-7

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