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. 1985 May 1;227(3):965–969. doi: 10.1042/bj2270965

The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilization.

B A Wolf, P G Comens, K E Ackermann, W R Sherman, M L McDaniel
PMCID: PMC1144928  PMID: 3890834

Abstract

Glucose-induced insulin secretion is thought to be mediated by submicromolar increases in intracellular Ca2+, although the intracellular processes are not well understood. We have used the previously characterized digitonin-permeabilized insulin-secreting pancreatic islet model to study the role of myo-inositol 1,4,5-trisphosphate (IP3), a putative second messenger for mobilization of intracellular Ca2+. Ca2+ efflux from the endoplasmic reticulum was studied with or without vanadate present to inhibit Ca2+ reuptake. IP3 (10 microM), at a free Ca2+ level of 0.06 microM, increased Ca2+ release by 30% and, when vanadate was present, by 50%. Maximal and half-maximal Ca2+ release was observed at 10 microM- and 2.5 microM-IP3, respectively. IP3 provoked a rapid release that was followed by slow reuptake. Reuptake was diminished in the presence of vanadate. Inositol 1,4-bisphosphate, inositol 1-phosphate and other phosphoinositide metabolites did not have any significant effect. Because increases in Ca2+ levels in the submicromolar range have been previously shown to induce insulin release in digitonin-permeabilized islets, our results are consistent with the concept of IP3 serving as a second messenger for insulin secretion.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agranoff B. W., Seguin E. B. Preparation of inositol triphosphate from brain: GLC of trimethylsilyl derivative. Prep Biochem. 1974;4(4):359–366. doi: 10.1080/00327487408068211. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J., Heslop J. P., Irvine R. F., Brown K. D. Inositol trisphosphate formation and calcium mobilization in Swiss 3T3 cells in response to platelet-derived growth factor. Biochem J. 1984 Aug 15;222(1):195–201. doi: 10.1042/bj2220195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  5. Best L., Malaisse W. J. Nutrient and hormone-neurotransmitter stimuli induce hydrolysis of polyphosphoinositides in rat pancreatic islets. Endocrinology. 1984 Nov;115(5):1814–1820. doi: 10.1210/endo-115-5-1814. [DOI] [PubMed] [Google Scholar]
  6. Biden T. J., Prentki M., Irvine R. F., Berridge M. J., Wollheim C. B. Inositol 1,4,5-trisphosphate mobilizes intracellular Ca2+ from permeabilized insulin-secreting cells. Biochem J. 1984 Oct 15;223(2):467–473. doi: 10.1042/bj2230467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bond G. H., Hudgins P. M. Inhibition of red cell Ca2+-ATPase by vanadate. Biochim Biophys Acta. 1980 Aug 14;600(3):781–790. doi: 10.1016/0005-2736(80)90480-0. [DOI] [PubMed] [Google Scholar]
  8. Burgess G. M., McKinney J. S., Irvine R. F., Berridge M. J., Hoyle P. C., Putney J. W., Jr Inositol 1,4,5-trisphosphate may be a signal for f-Met-Leu-Phe-induced intracellular Ca mobilisation in human leucocytes (HL-60 cells). FEBS Lett. 1984 Oct 15;176(1):193–196. doi: 10.1016/0014-5793(84)80939-4. [DOI] [PubMed] [Google Scholar]
  9. Clements R. S., Jr, Rhoten W. B. Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets. J Clin Invest. 1976 Mar;57(3):684–691. doi: 10.1172/JCI108325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Colca J. R., Brooks C. L., Landt M., McDaniel M. L. Correlation of Ca2+-and calmodulin-dependent protein kinase activity with secretion of insulin from islets of Langerhans. Biochem J. 1983 Jun 15;212(3):819–827. doi: 10.1042/bj2120819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Colca J. R., Kotagal N., Lacy P. E., Brooks C. L., Norling L., Landt M., McDaniel M. L. Glucose-stimulated protein phosphorylation in the pancreatic islet. Biochem J. 1984 Jun 1;220(2):529–537. doi: 10.1042/bj2200529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Colca J. R., Kotagal N., Lacy P. E., McDaniel M. L. Comparison of the properties of active Ca2+ transport by the islet-cell endoplasmic reticulum and plasma membrane. Biochim Biophys Acta. 1983 Apr 6;729(2):176–184. doi: 10.1016/0005-2736(83)90483-2. [DOI] [PubMed] [Google Scholar]
  13. Colca J. R., McDonald J. M., Kotagal N., Patke C., Fink C. J., Greider M. H., Lacy P. E., McDaniel M. L. Active calcium uptake by islet-cell endoplasmic reticulum. J Biol Chem. 1982 Jun 25;257(12):7223–7228. [PubMed] [Google Scholar]
  14. Downes C. P., Michell R. H. The polyphosphoinositide phosphodiesterase of erythrocyte membranes. Biochem J. 1981 Jul 15;198(1):133–140. doi: 10.1042/bj1980133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dunlop M. E., Larkins R. G. The role of calcium in phospholipid turnover following glucose stimulation in neonatal rat cultured islets. J Biol Chem. 1984 Jul 10;259(13):8407–8411. [PubMed] [Google Scholar]
  16. GRADO C., BALLOU C. E. Myo-inositol phosphates obtained by alkaline hydrolysis of beef brain phosphoinositide. J Biol Chem. 1961 Jan;236:54–60. [PubMed] [Google Scholar]
  17. Gershengorn M. C., Geras E., Purrello V. S., Rebecchi M. J. Inositol trisphosphate mediates thyrotropin-releasing hormone mobilization of nonmitochondrial calcium in rat mammotropic pituitary cells. J Biol Chem. 1984 Sep 10;259(17):10675–10681. [PubMed] [Google Scholar]
  18. Hedeskov C. J. Mechanism of glucose-induced insulin secretion. Physiol Rev. 1980 Apr;60(2):442–509. doi: 10.1152/physrev.1980.60.2.442. [DOI] [PubMed] [Google Scholar]
  19. Hirata M., Suematsu E., Hashimoto T., Hamachi T., Koga T. Release of Ca2+ from a non-mitochondrial store site in peritoneal macrophages treated with saponin by inositol 1,4,5-trisphosphate. Biochem J. 1984 Oct 1;223(1):229–236. doi: 10.1042/bj2230229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Irvine R. F., Brown K. D., Berridge M. J. Specificity of inositol trisphosphate-induced calcium release from permeabilized Swiss-mouse 3T3 cells. Biochem J. 1984 Aug 15;222(1):269–272. doi: 10.1042/bj2220269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Joseph S. K., Williams R. J., Corkey B. E., Matschinsky F. M., Williamson J. R. The effect of inositol trisphosphate on Ca2+ fluxes in insulin-secreting tumor cells. J Biol Chem. 1984 Nov 10;259(21):12952–12955. [PubMed] [Google Scholar]
  22. Laychock S. G. Identification and metabolism of polyphosphoinositides in isolated islets of Langerhans. Biochem J. 1983 Oct 15;216(1):101–106. doi: 10.1042/bj2160101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McDaniel M. L., Colca J. R., Kotagal N., Lacy P. E. A subcellular fractionation approach for studying insulin release mechanisms and calcium metabolism in islets of Langerhans. Methods Enzymol. 1983;98:182–200. doi: 10.1016/0076-6879(83)98149-1. [DOI] [PubMed] [Google Scholar]
  24. Rosenberry T. L., Chen J. F., Lee M. M., Moulton T. A., Onigman P. Large scale isolation of human erythrocyte membranes by high volume molecular filtration. J Biochem Biophys Methods. 1981 Jan;4(1):39–48. doi: 10.1016/0165-022x(81)90004-x. [DOI] [PubMed] [Google Scholar]
  25. Seiffert U. B., Agranoff B. W. Isolation and separation of inositol phosphates from hydrolysates of rat tissues. Biochim Biophys Acta. 1965 Jun 1;98(3):574–581. doi: 10.1016/0005-2760(65)90154-2. [DOI] [PubMed] [Google Scholar]
  26. Sherman W. R., Leavitt A. L., Honchar M. P., Hallcher L. M., Phillips B. E. Evidence that lithium alters phosphoinositide metabolism: chronic administration elevates primarily D-myo-inositol-1-phosphate in cerebral cortex of the rat. J Neurochem. 1981 Jun;36(6):1947–1951. doi: 10.1111/j.1471-4159.1981.tb10819.x. [DOI] [PubMed] [Google Scholar]
  27. Shukla S. D., Coleman R., Finean J. B., Michell R. H. Are polyphosphoinositides associated with glycophorin in human erythrocyte membranes? Biochem J. 1979 May 1;179(2):441–444. doi: 10.1042/bj1790441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wollheim C. B., Sharp G. W. Regulation of insulin release by calcium. Physiol Rev. 1981 Oct;61(4):914–973. doi: 10.1152/physrev.1981.61.4.914. [DOI] [PubMed] [Google Scholar]

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