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Regulatory effect of 1,25-dihydroxyvitamin D3 on insulin release and calcium handling via the phospholipid pathway in islets from vitamin D-deficient rats

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Abstract

The effect of 10−8 M 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] on the phosphoinositide pathway, was studied on [3H] inositol and 45Ca2+ efflux and on insulin release of islets from vitamin D-deficient rats, during an acetylcholine (Ach) stimulus in perifusion. The insulin release, which was low in vitamin D-deficient rats, was enhanced by this treatment. The 3H flux, reflecting phosphoinositide breakdown, was also increased. The 45Ca2+ flux was stimulated both during the first 14 min peak (mobilization of IP3-sensitive reticular Ca2+ stores) and during the following sustained small elevation of 45Ca2+ flux, reflecting protein kinase C (PKC) activation and consequently increased phosphorylation of Ca2+ channel proteins. These effects were larger during perifusions performed in the presence of glucose which is known to open Ca2+ channels, suggesting a synergistic influence of glucose and 1,25(OH)2D3. This positive influence of 1,25(OH)2D3 on Ca2+ entry by Ca2+ channels was confirmed by the use of nifedipine — a Ca2+ channel blocker-which suppressed the 45Ca2+ flux and lowered insulin secretion. Moreover, the sustained 45Ca2+ flux also disappeared in islets from vitamin D-deficient rats supplemented by 1,25(OH)2D3 but perifused without extracellular Ca2+, supporting the hypothesis of 1,25(OH)2D3-induced activation of PKC. Thus, 1,25(OH)2D3 may provide supplementary calcium to the B cell by regulating the intracellular signalling processes involving phospholipid metabolism, PKC induction, Ca2+ mobilization and Ca2+ entry by Ca2+ channels.

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References

  1. Minghetti P.P., Norman A.W. 1,25(OH)2-vitamin D3 receptors: gene regulation and genetic circuity. FASEB J. 2: 3043, 1988.

    PubMed  CAS  Google Scholar 

  2. Norman A., Roth J., Orci L. The vitamin D endocrine system: steroid metabolism, hormone receptors and biological response. Endocr. Rev. 3: 331,1982.

    Article  PubMed  CAS  Google Scholar 

  3. Rasmussen H., Matsumoto T., Fontaine O., Goodman D.B.P. Role of change in membrane lipid structure in the action of 1,25-dihydroxyvitamin D3. Fed Proc. 41: 72, 1982.

    PubMed  CAS  Google Scholar 

  4. Nemere I., Norman A.W.. Steroid hormone actions at the plasma membrane: induced calcium uptake and exocytotic events. Mol. Cell. Endocrinol. 80: C165, 1991.

    Article  PubMed  CAS  Google Scholar 

  5. Lieberherr M., Grosse B., Duchambon P., Drucke T. A functional cell surface type receptor is required for the early action of 1,25-dihydroxyvitamin D3 on the phosphoinositide metabolism in rat enterocytes. J. Biol. Chem. 264: 20403, 1989.

    PubMed  CAS  Google Scholar 

  6. Wali R.K, Baum C.L., Sitrin M.D., Brasitus T.A. 1.25(OH)2D3 vitamin-D3 stimulates membrane phosphoinositide turnover, activate protein kinase C and increases cytosolic calcium in rat colonic epithelium. J. Clin. Invest. 85: 1296, 1990.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Wali R.K., Bolt M.J.G., Tien X.-Y., Brasitus T.A., Sitrin M.D. Differential effect of 1,25-dihydroxycholecalciferol on phosphoinositide turnover in the antipodal plasma membranes of colonic epithelial cells. Biochem. Biophys. Res. Commun. 187: 1128, 1992.

    Article  PubMed  CAS  Google Scholar 

  8. De Boland A.R., Boland R.L. Rapid changes in skeletal muscle uptake induced in vitro by 1,25-dihydroxyvitamin D3 are suppressed by calcium channels blockers. Endocrinology 120: 1858, 1987.

    Article  PubMed  Google Scholar 

  9. Caffrey J.M., Farach-Carson M.C. Vitamin D3 metabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. J. Biol. Chem. 264: 20265, 1989.

    PubMed  CAS  Google Scholar 

  10. Walters M.R. Newly identified actions of the vitamin D endocrine system. Endocr. Res. 13: 719, 1992.

    CAS  Google Scholar 

  11. Christakos S., Norman A.W. Studies for the mode of action of calciferol XVIII. Evidence for a specific high affinity binding protein for 1,25-dihydroxyvitamin D3 in chick kidney and pancreas. Biochem. Biophys. Res. Commun. 89: 56,1979.

    Article  PubMed  CAS  Google Scholar 

  12. Ishida H., Norman A.W. Demonstration of high affinity receptor for 1,25-dihydroxyvitamin in rat pancreas. Mol. Cell. Endocrinol. 60: 109, 1988.

    Article  PubMed  CAS  Google Scholar 

  13. Christakos S., Friedlander E.J., Frandsen B.R., Norman A.W. Studies on the mode of action of calciferol. XIII Development of a radioimmunoassay for vitamin D-dependent chick intestinal calcium binding protein and tissue distribution. Endocrinology 104: 1495, 1979.

    Google Scholar 

  14. Thomasset M., Parke CO., Cuisinier-Gleizes P. Rat calcium binding proteins: distribution, development and vitamin D dependence. Am. J. Physiol. 243: E483, 1982.

    PubMed  CAS  Google Scholar 

  15. Bourlon P.M., Billaudel B., Thomasset M., Sutter B.Ch.J., Faure A Effects of vitamin D3 deficiency and repletion with 1,25-dihydroxyvitamin D3 on calbindin 28K in the rat endocrine pancreas. In: Norman A.W., Bouillon R., Thomasset, M. (Eds.), Vitamin D, Gene regulation structure Function Analysis and Clinical Application, De Gruyter, 1991, p. 627.

  16. Cade C., Norman A.W. Rapid normalization/stimulation by 1,25 dihydroxyvitamin D3 of insulin secretion and glucose tolerance in the vitamin D-deficient rat. Endocrinology 120: 1490, 1987.

    Article  PubMed  CAS  Google Scholar 

  17. Kadowaki S., Norman A.W. Demonstration that the vitamin D metabolite 1,25(OH)2-vitamin D3 and not 24R,25(OH)2-vitamin D3 is essential for normal insulin secretion in the perfused rat pancreas. Diabetes 34: 315, 1985.

    Article  PubMed  CAS  Google Scholar 

  18. Faure A., Sutter B.Ch.J., Billaudel B. Is 1,25-dihydroxyvitamin D3 the specific vitamin D3 metabolite active on insulin release and calcium handling by islets from vitamin D3-deprived rats? Diabète Metab. 17: 271, 1991.

    PubMed  CAS  Google Scholar 

  19. Billaudel B., Faure A., Labriji-Mestaghanmi H., Sutter B.Ch.J. Direct in vitro effect of 1,25-dihydroxyvitamin D3 on islets insulin secretion in vitamin deficient rats: influence of vitamin D3 pretreatment. Diabète Metab. 15: 85, 1989.

    PubMed  CAS  Google Scholar 

  20. Billaudel B., Faure A., Sutter B.Ch.J. Effect of 1,25-dihydroxyvitamin D3 on isolated islets from viitamin D3-deprived rats. Am. J. Physiol. 258: E643, 1990.

    PubMed  CAS  Google Scholar 

  21. Billaudel B., Delbancut A., Sutter B.Ch.J., Faure, A. Stimulatory effect of 1,25-dihydroxyvitamin D3 on calcium handling and insulin secretion by islets from vitamin D3-deficient rats. Steroids 58: 335, 1993.

    Article  PubMed  CAS  Google Scholar 

  22. Herbas T., Akalin S., Koray Z., Gedik O. Lack of effect of 1,25(OH)2D3 administration on glucose tolerance and insulin secretion in normal man. In: Norman A.W., Bouillon R. and Thomasset M. (de Gruyter) (Eds.) Vitamin D, Gene regulation Structure-Function. Analysis and Clinical Application, 1991, p.333.

  23. Chertow B.S., Sivitz W.I., Baranetsky N.G., Clark S.A., Waite A., DeLuca H.F. Cellular mechanisms of insulin release: the effects of vitamin D deficiency and repletion on rat insulin secretion. Endocrinology 113: 1511, 1983.

    Article  PubMed  CAS  Google Scholar 

  24. Lacy P.E., Kostianovsky M. Method for the isolation of intact islets of Langerhans from pancreas. Diabetes 16: 35, 1967.

    PubMed  CAS  Google Scholar 

  25. Labriji-Mestaghanmi H., Billaudel B., Gamier P.E., Malaisse W.J., Sutter B.Ch.J. Vitamin D and pancreatic islet function: I. Time course for changes in insulin secretion and content during vitamin D deprivation and repletion. J. Endocrinol. Invest. 11: 577, 1988.

    Article  PubMed  CAS  Google Scholar 

  26. Herbert V., Lau K.S., Gottlieb C.W., Bleicher S.J. Coated charcoal immunoassay of insulin. J. Clin. Endocrinol. Metab. 122: 1375, 1965.

    Article  Google Scholar 

  27. Zawalich W.S., Diaz V.A., Zawalich K.C. Influence of cAMP and calcium on 3H inositol efflux, inositol phosphate accumulation, and insulin release from isolated rat islets. Diabetes 37: 1478, 1988.

    Article  PubMed  CAS  Google Scholar 

  28. Mathias P.C.F., Carpinelli A.R., Billaudel B., Garcia-Morales P., Valverde I., Malaisse W.J. Cholinergic stimulation of ion fluxes in pancreatic islets. Biochem. Pharmacol. 34: 3451, 1985.

    Article  PubMed  CAS  Google Scholar 

  29. Herchuelz A., Couturier E., Malaisse W.J. Regulation of calcium fluxes in pancreatic islets: glucose-induced calcium-calcium exchange. Am. J. Physiol. 238: E96, 1980.

    PubMed  CAS  Google Scholar 

  30. Boschero A.C., Bordin S., Herchuelz A., Lebrun, P. Effect of glucose on 45Ca2+ outflow cytosolic Ca2+ concentration and insulin release from freshly isolated and cultured adult rat islets. Cell Calcium 11: 603, I990.

    Article  Google Scholar 

  31. Mathias P.C.F., Best L., Malaisse W.J. Stimulation by glucose and carbamylcholine of phospholipase C in pancreatic islets. Cell Biochem. Funct. 3: 173, 1985.

    Article  PubMed  CAS  Google Scholar 

  32. Prentky M., Biden T.J. Janjic D., Irvine R.F., Berridge M.J., Wollheim C.B. Rapid mobilization of Ca2+ from rat insulinomic microsomes by inositol-1,4,5-triphosphate. Nature 309: 562, 1984.

    Article  Google Scholar 

  33. Gylfe E. Carbachol induces sustained glucose-dependent oscillations of cytoplasmic Ca2+ in hyperpolarized pancreatic B cells. Pflügers Arch. 479: 639, 1991.

    Article  Google Scholar 

  34. Wang J.L., Corbett J.A., Marshall C.A., McDaniel M.L. Glucose-induced insulin from purified B-cells. A role for modulation of Ca2+ influx by cAMP and protein kinase C-dependent signal transduction pathways. J. Biol. Chem. 268: 7785, 1993.

    PubMed  CAS  Google Scholar 

  35. Clark R.B., Love J.T., Sgroi D., Linegenheld E., Sha’afi R. The protein kinase C inhibitor, H-7, inhibits antigen and IP-2-induced proliferation of murine T cell lines. Biochem. Biophys. Res. Commun. 145: 666, 1987.

    Article  PubMed  CAS  Google Scholar 

  36. Rajan A.S., Aguilar-Bryan L., Nelson D.A., Yaney G.C., Hsu W.K., Boyd III A.E.. Ion channels and insulin secretion. Diabetes 13: 340, 1990.

    CAS  Google Scholar 

  37. Henquin J.C., Meissner H.P. The ionic, electrical and secretory effects of endogenous cyclicadenosine monophosphate in mouse pancreatic B cells: studies with forskolin. Endocrinology 115: 1125, 1984.

    Article  PubMed  CAS  Google Scholar 

  38. Nilsson T., Arkhammar P., Halberg A., Hellman B., Berggren P.O. Extracellular Ca2+ induced a rapid increase in cytoplasmic free Ca2+ in pancreatic B-cells. Biochem. J. 248: 329, 1987.

    PubMed Central  PubMed  CAS  Google Scholar 

  39. Prentky M., Matschinsky F.M. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanism of insulin secretion. Physiol. Rev. 67: 1185, 1987.

    Google Scholar 

  40. Hii C.S.T., Jones P.M., Persaud S.J., Howell S.L. A reassessment of the role of protein kinase C in glucose stimulated insulin secretion. Biochem. J. 246: 489, 1987.

    PubMed Central  PubMed  CAS  Google Scholar 

  41. Wollheim C.B., Siegel E.G., Sharp G.W.G. Dependency of acetylcholine-induced insulin release on Ca++ uptake by rat pancreatic islets. Endocrinology 107: 924, 1980.

    Article  PubMed  CAS  Google Scholar 

  42. Biden T.V., Prugue M.L., Davison A.G.L. Evidence for phosphatidylinositol hydrolysis in pancreatic islets stimulated with carbamoylcholine. Kinetic analysis of inositol polyphosphate metabolism. Biochem. J. 285: 541, 1992.

    PubMed Central  PubMed  CAS  Google Scholar 

  43. Rorsman P., Arkhammar P., Berggren O. Voltage activated Na+ currents and their suppression by Phorbol ester in clonal insulin-producing RINm5F cells. Am. J. Physiol. 251: C919, 1986.

    Google Scholar 

  44. Peter-Riesch B., Fathi M., Schlegel W., Wollheim C.B. Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets. J. Clin. Invest. 81: 1154, 1988.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Chisholm J.C., Kirn S., Tashjian A.H. Modulation by 1,25-dihydroxycholecalciferol on the acute change in cytosolic free calcium induced by thyrotropin-releasing hormone in GH4C-1 pituitary cells. J. Clin Invest. 81: 661, 1988.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  46. d’Embden M.C., Wark J.D. Vitamin D enhanced thyrotrophin release from rat pituitary cells: effect of Ca2+, dihydropyridines and ionomycin. J. Endocrinol. 121: 441, 1989.

    Article  Google Scholar 

  47. Bellido T., Moreli S., Fernandez L.M., Boland R. Evidence for the participation of protein kinase-C and 3′, 5′-cyclic AMP dependent protein kinase in the stimulation of muscle cell proliferation by 1,25-dihydroxyvitamin-D3. Mol. Cell. Endocrinol. 90: 231, 1993.

    Article  PubMed  CAS  Google Scholar 

  48. Tornquist K. Pretreatment with 1,25-dihydroxycholecalciferol enhanced thyrotropin-releasing hormone-induced and inositol 1,4, 5-triphosphate-induced release of sequestered Ca2+ in permeabilized GH4C-1 pituitary cells. Endocrinology 131: 1677, 1992.

    PubMed  CAS  Google Scholar 

  49. Mezzetti G., Moni M.G., Perneco Casolo L., Piccinini G., Moruzzi M.S. 1.25-dihydroxycholecalciferol-dependent calcium uptake by mouse mammary gland in culture. Endocrinology 122: 389, 1988.

    Article  PubMed  CAS  Google Scholar 

  50. Sugimoto T., Ritter C., Ried I., Morrissey J., Slatopolsky E. Effect of 1,25-dihydroxyvitamin D3 on cytosolic calcium in dispersed parathyroid cells. Kidney Int. 33: 850, 1988.

    Article  PubMed  CAS  Google Scholar 

  51. Suzuki M., Kawaguchi Y., Momose M., Morita T., Yokohama K., Miyahara T. 1,25-dihydroxyvitamin D stimulates sodium-dependent phosphate transport by renal outer cortical brush-border membrane vesicles by directly affecting membrane fluidity. Biochem. Biophys. Res. Commun. 150: 1193,1988.

    Article  PubMed  CAS  Google Scholar 

  52. Fernandez L.M., Massheimer V., de Boland A.R. Cyclic AMP-dependent membrane proteins phosphorylation and calmodulin binding are involved in the rapid stimulation of muscle calcium uptake by 1,25-dihydroxitamin D3. Calcif. Tissue Int. 47: 314, 1990.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratoire d’Endocrinologie, Université de Bordeaux I, Avenue des Facultés, 33405, Bordeaux, Talence Cedex, France

    Bernard Billaudel M.D., P. M. D. Bourlon, B. Ch. J. Sutter & A. G. Faure-Dussert

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  1. Bernard Billaudel M.D.
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  2. P. M. D. Bourlon
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  3. B. Ch. J. Sutter
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  4. A. G. Faure-Dussert
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Billaudel, B., Bourlon, P.M.D., Sutter, B.C.J. et al. Regulatory effect of 1,25-dihydroxyvitamin D3 on insulin release and calcium handling via the phospholipid pathway in islets from vitamin D-deficient rats. J Endocrinol Invest 18, 673–682 (1995). https://doi.org/10.1007/BF03349788

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