, Volume 17, Issue 2, pp 103–108 | Cite as

Ca2+ handling of rat pancreatic β-cells exposed to ryanodine, caffeine, and glucagon



Reported species differences in the stimulus-secretion coupling of insulin release made it important to compare the Ca2+ handling of rat β-cells with that previously observed in mice. Single β-cells and small aggregates were prepared from pancreatic islets of Wistar rats, attached to cover slips and then used for measuring the cytoplasmic Ca2+ concentration ([Ca2+]i) with the ratiometric fura-2 technique. Glucose (11 mM) induced slow oscillations of [Ca2+]i similar to those seen in other species, including humans. Comparison of the oscillations in rat β-cells with those previously described in mouse revealed that there was a slightly lower frequency and an increased tendency to transformation into sustained [Ca2+]i in response to glucagon or caffeine. Ryanodine (5–20 µM) did not affect existing oscillations but sometimes restored rhythmic activity in the presence of caffeine. Stimulation with glucose resulted not only in oscillations but also in transients of [Ca2+]i sometimes appearing in synchrony in adjacent β-cells and disappearing after the addition of 200 nM thapsigargin 20 mM caffeine. The frequency of transients recorded in a medium containing glucagon and methoxyverapamil was higher than seen under similar conditions in mouse β-cells. Although exhibiting some differences compared with mouse β-cells, rat β-cells also have an intrinsic ability to oscillate and to generate the transients of [Ca2+]i that are supposed to synchronize the rhythmicity of the islets in the pancreas.

Key Words

Ca2+ oscillations caffeine glucagon rat β-cells ryanodine 


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  1. 1.
    Wollheim, C. B. and Sharp, G. W. (1981). Physiol. Rev. 61, 914–973.PubMedGoogle Scholar
  2. 2.
    Hellman, B., Gylfe, E., Grapengiesser, E., Lund, P.-E. and Berts, A. (1992). Biochim. Biophys. Acta 1113, 295–305.PubMedGoogle Scholar
  3. 3.
    Dryselius, S., Grapengiesser, E., Hellman, B., and Gylfe, E. (1999). Am. J. Physiol. 276, E512-E518.PubMedGoogle Scholar
  4. 4.
    Grapengiesser, E., Gylfe, E., and Hellman, B. (1988). Biochem. Biophys. Res. Commun. 151, 1299–1304.PubMedCrossRefGoogle Scholar
  5. 5.
    Bergsten, P., Grapengiesser, E., Gylfe, E., Tengholm, A., and Hellman, B. (1994). J. Biol. Chem. 269, 8749–8753.PubMedGoogle Scholar
  6. 6.
    Liu, Y. J., Grapengiesser, E., Gylfe, E., and Hellman, B. (1996). Arch. Biochem. Biophys. 334, 295–302.PubMedCrossRefGoogle Scholar
  7. 7.
    Grapengiesser, E., Gylfe, E., Dansk, H., and Hellman, B. (2001). Pancreas 23, 387–392.PubMedCrossRefGoogle Scholar
  8. 8.
    Ahmed, M. and Grapengiesser, E. (2001). Endocrine 15, 73–78.PubMedCrossRefGoogle Scholar
  9. 9.
    Hellman, B., Grapengiesser, E., and Gylfe, E. (2000). Diabetes Res. Clin. Pract. 50(Suppl. 1), S148.Google Scholar
  10. 10.
    Wang, J. L. and McDaniel, M. L. (1990). Biochem. Biophys. Res. Commun. 166, 813–818.PubMedCrossRefGoogle Scholar
  11. 11.
    Herchuelz, A., Pochet, R., Pastiels, C., and Van Praet, A. (1991). Cell Calcium 12, 577–586.PubMedCrossRefGoogle Scholar
  12. 12.
    Theler, J.-M., Mollard, P., Guérineau, N., Vacher, P., Pralong, W. F., Schlegel, W., and Wollheim, C. B. (1992). J. Biol. Chem. 267, 18,110–18,117.Google Scholar
  13. 13.
    Yada, T., Nakata, M., Shiraishi, T., and Kakei, M. (1999). Br. J. Pharmacol. 126, 1205–1213.PubMedCrossRefGoogle Scholar
  14. 14.
    Longo, E. A., Tornheim, K., Deeney, J. T., Varnum, B. A., Tillotson, D., Prentki, M., and Corkey, B. E. (1991). J. Biol. Chem. 266, 9314–9319.PubMedGoogle Scholar
  15. 15.
    Martin, F., Reig, J. A., and Soria, B. (1995). J. Mol. Endocrinol. 15, 177–185.PubMedGoogle Scholar
  16. 16.
    Lenzen, S. (1979). Am. J. Physiol. 236, E391-E400.PubMedGoogle Scholar
  17. 17.
    Berglund, O. (1980). Acta Endocrinol. (Copenh.) 93, 54–60.Google Scholar
  18. 18.
    Ma, Y. H., Wang, J., Rodd, G. G., Bolaffi, J. L., and Grodsky, G. M. (1995). Eur. J. Endocrinol. 132, 370–376.PubMedGoogle Scholar
  19. 19.
    Zawalich, W. S. and Zawalich, K. C. (1996). Am. J. Physiol. 271, E409-E416.PubMedGoogle Scholar
  20. 20.
    Antunes, C. M., Salgado, A. P., Rosario, L. M., and Santos, R. M. (2000). Diabetes 49, 2028–2038.PubMedCrossRefGoogle Scholar
  21. 21.
    De Smedt, H., Missiaen, L., Parys, J. B., Bootman, M. D., Mertens, L., Van Den Bosch, L., and Casteels, R. (1994). J. Biol. Chem. 269, 21,691–21,698.Google Scholar
  22. 22.
    Blondel, O., Takeda, J., Janssen, H., Seino, S., and Bell, G. I. (1993). J. Biol. Chem. 268, 11,356–11,363.Google Scholar
  23. 23.
    Lee, B., Bradford, P. G., and Laychock, S. G. (1998). J. Mol. Endocrinol. 21, 31–39.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee, B., Jonas, J. C., Weir, G. C., and Laychock, S. G. (1999). Endocrinology 140, 2173–2182.PubMedCrossRefGoogle Scholar
  25. 25.
    Hellman, B., Gylfe, E., Bergsten, P., Grapengiesser, E., Lund, P.-E., Berts, A., Tengholm, A., Pipeleers, D. G., and Ling, Z. (1994). Diabetologia 37(Suppl. 2), S11-S20.PubMedCrossRefGoogle Scholar
  26. 26.
    Dryselius, S., Lund, P.-E., Gylfe, E., and Hellman, B. (1994). Biochem. Biophys. Res. Commun. 205, 880–885.PubMedCrossRefGoogle Scholar
  27. 27.
    Eberhardson, M., Tengholm, A., and Grapengiesser, E. (1996). Biochim. Biophys. Acta 1283, 67–72.PubMedCrossRefGoogle Scholar
  28. 28.
    Grapengiesser, E., Gylfe, E., and Hellman, B. (1989). Acta Physiol. Scand. 136, 113–119.PubMedCrossRefGoogle Scholar
  29. 29.
    Tengholm, A., McClenaghan, N., Grapengiesser, E., Gylfe, E., and Hellman, B. (1992). Biochim. Biophys. Acta 1137, 243–247.PubMedCrossRefGoogle Scholar
  30. 30.
    Ahmed, M., Grapengiesser, E., and Hellman, B. (1999). J. Endocrinol. 160, 191–195.PubMedCrossRefGoogle Scholar
  31. 31.
    Grapengiesser, E., Gylfe, E., and Hellman, B. (1992). Cell Calcium 13, 219–226.PubMedCrossRefGoogle Scholar
  32. 32.
    Sharp, G. W., Wiedenkeller, D. E., Kaelin, D., Siegel, E. G., and Wollheim, C. B. (1980). Diabetes 29, 74–77.PubMedCrossRefGoogle Scholar
  33. 33.
    Hellman, B., Gylfe, E., Grapengiesser, E., Lund, P.-E., and Marcström, A. (1991). In: Nutrient regulation of insulin secretion. Flatt, P. R. (ed.) Portland Press: London.Google Scholar
  34. 34.
    Yada, T., Itoh, K., and Nakata, M. (1993). Endocrinology 133, 1685–1692.PubMedCrossRefGoogle Scholar
  35. 35.
    Yaekura, K. and Yada, T. (1998). Am. J. Physiol. 274, C513-C521.PubMedGoogle Scholar
  36. 36.
    Holz, G. G., Leech, C. A., Heller, R. S., Castonguay, M., and Habener, J. F. (1999). J. Biol. Chem. 274, 14,147–14,156.Google Scholar
  37. 37.
    Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993). Science 259, 370–373.PubMedCrossRefGoogle Scholar
  38. 38.
    Kato, I., Yamamoto, Y., Fujimura, M., Noguchi, N., Takasawa, S., and Okamoto, H. (1999). J. Biol. Chem. 274, 1869–1872.PubMedCrossRefGoogle Scholar
  39. 39.
    Worley, J. F. III, McIntyre, M. S., Spencer, B., and Dukes, I. D. (1994). J. Biol. Chem. 269, 32,055–32,058.Google Scholar
  40. 40.
    Miura, Y., Henquin, J. C., and Gilon, P. (1997). J. Physiol. 503, 387–398.PubMedCrossRefGoogle Scholar
  41. 41.
    Islam, M. S., Larsson, O., Nilsson, T., and Berggren, P. O. (1995). Biochem. J. 306, 679–686.PubMedGoogle Scholar
  42. 42.
    Gamberucci, A., Fulceri, R., Pralong, W., Bánhegyi, G., Marcolongo, P., Watkins, S. L., and Benedetti, A. (1999). FEBS Lett. 446, 309–312.PubMedCrossRefGoogle Scholar
  43. 43.
    Butcher, R. W. and Sutherland, E. W. (1962). J. Biol. Chem. 237, 1244–1250.PubMedGoogle Scholar
  44. 44.
    Islam, M. S., Leibiger, I., Leibiger, B., Rossi, D., Sorrentino, V., Ekstrom, T. J., Westerblad, H., Andrade, F. H., and Berggren, P. O. (1998). Proc. Natl. Acad. Sci. USA 95, 6145–6150.PubMedCrossRefGoogle Scholar
  45. 45.
    Tengholm, A., Hellman, B., and Gylfe, E. (2000). Cell Calcium 27, 43–51.PubMedCrossRefGoogle Scholar
  46. 46.
    Chen, T. H., Lee, B., Yang, C., and Hsu, W. H. (1996). Life Sci. 58, 983–990.PubMedCrossRefGoogle Scholar
  47. 47.
    Grapengiesser, E., Gylfe, E., and Hellman, B. (1999). Biochem. Biophys. Res. Commun. 254, 436–439.PubMedCrossRefGoogle Scholar
  48. 48.
    Hagar, R. E., Burgstahler, A. D., Nathanson, M. H., and Ehrlich, B. E. (1998). Nature 396, 81–84.PubMedCrossRefGoogle Scholar
  49. 49.
    Lernmark, Å. (1974). Diabetologia 10, 431–438.PubMedCrossRefGoogle Scholar
  50. 50.
    Hellman, B. (1959). Acta Endocrinol. (Copenh.) 32, 92–112.Google Scholar
  51. 51.
    Berts, A., Gylfe, E., and Hellman, B. (1995). Biochem. Biophys. Res. Commun. 208, 644–649.PubMedCrossRefGoogle Scholar
  52. 52.
    Grynkiewicz, G., Poenie, M., and Tsien, R. Y. (1985). J. Biol. Chem. 260, 3440–3450.PubMedGoogle Scholar
  53. 53.
    Gylfe, E., Grapengiesser, E., and Hellman, B. (1991). Cell Calcium 12, 229–240.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  1. 1.Department of Medical Cell BiologyUppsala UniversityUppsalaSweden

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