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Pflügers Archiv

, Volume 365, Issue 1, pp 21–28 | Cite as

Calcium-antagonists and islet function

VI. Effect of barium
  • G. Somers
  • G. Devis
  • E. Van Obberghen
  • W. J. Malaisse
Article

Summary

The modality of Ba2+-induced insulin release was investigated in the isolated perfused rat pancreas. The insulinotropic action of Ba2+ was antagonized by Ca2+, Mg2+ and verapamil, and enhanced by EGTA, theophylline, glucose and cytochalasin B. Likewise the net uptake of133Ba2+ by isolated islets was inhibited by Ca2+, Mg2+ and verapamil. Glucose increased133Ba2+ net uptake, but only when sufficient Ba2+ had accumulated in the islets. Theophylline failed to affect133Ba2+ net uptake. These data suggest that (i) Ba2+-induced insulin release is dependent on the accumulation of this cation in the B-cell; (ii) Ba2+ inward transport in the B-cell occurs through a verapamil-sensitive channel characterized by competition between Ba2+, Ca2+ and Mg2+; and (iii) the enhancing effect of theophylline upon insulin release could be due to an intracellular translocation of alkaline-earth cations rather than to an increase in their net uptake. The present findings also support the idea that insulin release can be triggered by the accumulation of suitable divalent cations in a critical site of the B-cell, leading to the activation of a cytochalasin B-responsive effector system.

Key words

Insulin secretion Barium calcium Magnesium Verapamil 

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References

  1. 1.
    Brisson, G. R., Malaisse, W. J.: The stimulus-secretion coupling of glucose-induced insulin release. XI. Effects of theophylline and epinephrine on45Ca efflux from perifused islets. Metabolism22, 455–465 (1973)Google Scholar
  2. 2.
    Brisson, G. R., Malaisse-Lagae, F., Malaisse, W. J.: The stimulus-secretion coupling of glucose-induced insulin release. VII. A proposed site of action for adenosine-3′,5′-cyclic monophosphate. J. clin. Invest.51, 232–241 (1972)Google Scholar
  3. 3.
    Devis, G., Somers, G., Malaisse, W. J.: Stimulation of insulin release by calcium. Biochem. biophys. Res. Commun.67, 525–529 (1975)Google Scholar
  4. 4.
    Devis, G., Somers, G., Van Obberghen, E., Malaisse, W. J.: Calcium antagonists and islet function. I. Inhibition of insulin release by verapamil. Diabetes24, 547–551 (1975)Google Scholar
  5. 5.
    Devis, G., Somers, G., Van Obberghen, E., Malaisse, W. J.: Competition and synergism between calcium and barium upon insulin release. Diabetologia11, 338 (1975)Google Scholar
  6. 6.
    Fleckenstein, A., Grün, G., Tritthart, H., Byon, K.: Uterus-relaxation durch hochaktive Ca2+-antagonistische Hemmstoffe der elektro-mechanischen Koppelung wie Isoptin (Verapamil, Iproveratril), Substanz D600 and Segontin (Prenylamin). Klin. Wschr.49, 32–41 (1971)Google Scholar
  7. 7.
    Hales, C. N.: Ion fluxes and membrane function in β-cells and adipocytes. Acta diabet. lat.7, (Suppl.1), 64–75 (1970)Google Scholar
  8. 8.
    Hales, C. N., Milner, R. D. G.: Cations and the secretion of insulin from rabbit pancreas in vitro. J. Physiol. (Lond.)199, 177–187 (1968)Google Scholar
  9. 9.
    Kolhardt, M., Haastert, H. P., Krause, H.: Evidence of nonspecificity of the Ca channel in mammalian myocardial fibre membranes. Substitution of Ca by Sr, Ba or Mg as charge carriers. Pflügers Arch.342, 125–136 (1973)Google Scholar
  10. 10.
    Levy, J., Herchuelz, A., Sener, A., Malaisse, W. J.: Inhibition by verapamil of calcium influx in the B-cell. Diabetes24, 400 (1975)Google Scholar
  11. 11.
    Malaisse, W. J., Brisson, G. R., Baird, L. E.: Stimulus-secretion coupling of glucose-induced insulin release. X. Effect of glucose on45Ca efflux from perifused islets. Amer. J. Physiol.224, 389–394 (1973)Google Scholar
  12. 12.
    Malaisse, W. J., Brisson, G. R., Malaisse-Lagae, F.: The stimulus-secretion coupling of glucose-induced insulin release. I. Interaction of epinephrine and alkaline earth cations. J. Lab. clin. Med.76, 895–902 (1970)Google Scholar
  13. 13.
    Malaisse, W. J., Devis, G., Pipeleers, D. G., Somers, G.: Calcium antagonists and islet function. IV. Effect of D600. Diabetologia12, 77–81 (1976)Google Scholar
  14. 14.
    Malaisse, W. J., Hager, D. L., Orci, L.: The stimulus-secretion coupling of glucose-induced insulin release. IX. The participation of the beta cell web. Diabetes21, 594–604 (1972)Google Scholar
  15. 15.
    Malaisse-Lagae, F., Malaisse, W. J.: Stimulus-secretion coupling of glucose-induced insulin release. III. Uptake of45calcium by isolated islets of Langerhans. Endocrinology88, 72–80 (1971)Google Scholar
  16. 16.
    Milner, R. D. G., Hales, C. N.: The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreas in vitro. Biochem. J.113, 473–479 (1969)Google Scholar
  17. 17.
    Orci, L., Gabbay, K. H., Malaisse, W. J.: Pancreatic beta-cell web: Its possible role in insulin secretion. Science175, 1128–1130 (1972)Google Scholar
  18. 18.
    Van Obberghen, E., Somers, G., Devis, G., Ravazzola, M., Malaisse-Lagae, F., Orci, L., Malaisse, W. J.: Dynamics of insulin release and microtubular-microfilamentous system. VII. Do microfilaments provide the motive force for the translocation and extrusion of beta granules? Diabetes24, 892–901 (1975)Google Scholar
  19. 19.
    Van Obberghen, E., Somers, G., Devis, G., Vaughan, G. D., Malaisse-Lagae, F., Orci, L., Malaisse, W. J.: Dynamics of insulin release and microtubular-microfilamentous system. I. Effect of cytochalasin B. J. clin. Invest.52, 1041–1051 (1973)Google Scholar
  20. 20.
    Wollheim, C. B., Blondel, B., Truheart, P. A., Renold, A. E., Sharp, G. W. G.: Calcium-induced insulin release in monolayer of the endocrine pancreas. Studies with ionophore A23187. J. biol. Chem.250, 1354–1360 (1975)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • G. Somers
    • 1
  • G. Devis
    • 1
  • E. Van Obberghen
    • 1
  • W. J. Malaisse
    • 1
  1. 1.Laboratory of Experimental MedicineBrussels UniversityBrusselsBelgium

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