Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1986 Sep 15;238(3):773–779. doi: 10.1042/bj2380773

A role for calcium in the breakdown of inositol phospholipids in intact and digitonin-permeabilized pancreatic islets.

L Best
PMCID: PMC1147203  PMID: 3541917

Abstract

Glucose (20 mM) and 4-methyl-2-oxopentanoate (10 mM) both caused a pronounced stimulation of insulin release and of [3H]inositol phosphate production in rat pancreatic islets prelabelled with myo-[3H]inositol. Secretory responses to these nutrients were markedly impaired by lowering the Ca2+ concentration of the incubation medium to 10(-4)M or less, whereas stimulated inositol phosphate production was sensitive to Ca2+ within the range 10(-6)-10(-4)M. Inositol phosphate formation in response to carbamoylcholine was also found to be dependent on the presence of 10(-5)M-Ca2+ or above. Raising the concentration of K+ in the medium resulted in a progressive, Ca2+-dependent stimulation of inositol phosphate production in islets, although no significant stimulation of insulin release was observed. In islets prelabelled with myo[3H]inositol, then permeabilized by exposure to digitonin, [3H]inositol phosphate production could be triggered by raising the Ca2+ concentration from 10(-7) to 10(-5)M. This effect was dependent on the concentration of ATP and the presence of Li+, and involved detectable increases in the levels of InsP3 and InsP2 as well as InsP. A potentiation of inositol phosphate production by carbamoylcholine was observed in permeabilized islets at lower Ca2+ concentrations, although nutrient stimuli were ineffective. No significant effects were observed with guanine nucleotides or with neomycin, although NADH produced a modest increase and adriamycin a small inhibition of inositol phosphate production in permeabilized islets. These results strongly suggest that Ca2+ ions play an important role in the stimulation of inositol lipid metabolism in islets in response to nutrient secretagogues, and that inositide breakdown may actually be triggered by Ca2+ entry into the islet cells.

Full text

PDF
773

Selected References

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

  1. Axen K. V., Schubart U. K., Blake A. D., Fleischer N. Role of Ca2+ in secretagogue-stimulated breakdown of phosphatidylinositol in rat pancreatic islets. J Clin Invest. 1983 Jul;72(1):13–21. doi: 10.1172/JCI110951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [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. Best L., Brooks K. J., Bolton T. B. Relationship between stimulated inositol lipid hydrolysis and contractility in guinea-pig visceral longitudinal smooth muscle. Biochem Pharmacol. 1985 Jul 1;34(13):2297–2301. doi: 10.1016/0006-2952(85)90785-3. [DOI] [PubMed] [Google Scholar]
  5. Best L., Malaisse W. J. Effects of nutrient secretagogues upon phospholipid metabolism in rat pancreatic islets. Mol Cell Endocrinol. 1983 Oct;32(2-3):205–214. doi: 10.1016/0303-7207(83)90083-7. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Best L., Malaisse W. J. Phosphatidylinositol and phosphatidic acid metabolism in rat pancreatic islets in response to neurotransmitter and hormonal stimuli. Biochim Biophys Acta. 1983 Jan 7;750(1):157–163. doi: 10.1016/0005-2760(83)90215-1. [DOI] [PubMed] [Google Scholar]
  8. Best L., Malaisse W. J. Phospholipids and islet function. Diabetologia. 1983 Oct;25(4):299–305. doi: 10.1007/BF00253189. [DOI] [PubMed] [Google Scholar]
  9. Best L., Malaisse W. J. Stimulation of phosphoinositide breakdown in rat pancreatic islets by glucose and carbamylcholine. Biochem Biophys Res Commun. 1983 Oct 14;116(1):9–16. doi: 10.1016/0006-291x(83)90373-x. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. COUPLAND R. E. The innervation of pan creas of the rat, cat and rabbit as revealed by the cholinesterase technique. J Anat. 1958 Jan;92(1):143–149. [PMC free article] [PubMed] [Google Scholar]
  12. Cockcroft S., Bennett J. P., Gomperts B. D. f-MetLeuPhe-induced phosphatidylinositol turnover in rabbit neutrophils is dependent on extracellular calcium. FEBS Lett. 1980 Jan 28;110(1):115–118. doi: 10.1016/0014-5793(80)80036-6. [DOI] [PubMed] [Google Scholar]
  13. Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
  14. Cockcroft S., Gomperts B. D. The ATP4- receptor of rat mast cells. Biochem J. 1980 Jun 15;188(3):789–798. doi: 10.1042/bj1880789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Colca J. R., Wolf B. A., Comens P. G., McDaniel M. L. Protein phosphorylation in permeabilized pancreatic islet cells. Biochem J. 1985 Jun 15;228(3):529–536. doi: 10.1042/bj2280529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Creba J. A., Downes C. P., Hawkins P. T., Brewster G., Michell R. H., Kirk C. J. Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones. Biochem J. 1983 Jun 15;212(3):733–747. doi: 10.1042/bj2120733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Downes P., Michell R. H. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: lipids in search of a function. Cell Calcium. 1982 Oct;3(4-5):467–502. doi: 10.1016/0143-4160(82)90031-8. [DOI] [PubMed] [Google Scholar]
  18. Grodsky G. M., Bennett L. L. Cation requirements for insulin secretion in the isolated perfused pancreas. Diabetes. 1966 Dec;15(12):910–913. doi: 10.2337/diab.15.12.910. [DOI] [PubMed] [Google Scholar]
  19. Harrington C. A., Eichberg J. Norepinephrine causes alpha 1-adrenergic receptor-mediated decrease of phosphatidylinositol in isolated rat liver plasma membranes supplemented with cytosol. J Biol Chem. 1983 Feb 25;258(4):2087–2090. [PubMed] [Google Scholar]
  20. Henquin J. C., Lambert A. E. Cationic environment and dynamics of insulin secretion. II. Effect of a high concentration of potassium. Diabetes. 1974 Dec;23(12):933–942. doi: 10.2337/diab.23.12.933. [DOI] [PubMed] [Google Scholar]
  21. Herchuelz A., Thonnart N., Sener A., Malaisse W. J. Regulation of calcium fluxes in pancreatic islets: the role of membrane depolarization. Endocrinology. 1980 Aug;107(2):491–497. doi: 10.1210/endo-107-2-491. [DOI] [PubMed] [Google Scholar]
  22. Hickman J. A., Chahwala S. B., Thompson M. G. Interaction of the antibiotic adriamycin with the plasma membrane. Adv Enzyme Regul. 1985;24:263–274. doi: 10.1016/0065-2571(85)90081-0. [DOI] [PubMed] [Google Scholar]
  23. Irvine R. F., Letcher A. J., Dawson R. M. Phosphatidylinositol-4,5-bisphosphate phosphodiesterase and phosphomonoesterase activities of rat brain. Some properties and possible control mechanisms. Biochem J. 1984 Feb 15;218(1):177–185. doi: 10.1042/bj2180177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Irvine R. F., Letcher A. J., Lander D. J., Downes C. P. Inositol trisphosphates in carbachol-stimulated rat parotid glands. Biochem J. 1984 Oct 1;223(1):237–243. doi: 10.1042/bj2230237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Lacy P. E., Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967 Jan;16(1):35–39. doi: 10.2337/diab.16.1.35. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Lin S. H., Fain J. N. Vasopressin and epinephrine stimulation of phosphatidylinositol breakdown in the plasma membrane of rat hepatocytes. Life Sci. 1981 Nov 2;29(18):1905–1912. doi: 10.1016/0024-3205(81)90523-3. [DOI] [PubMed] [Google Scholar]
  29. Litosch I., Wallis C., Fain J. N. 5-Hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands. Evidence for a role of GTP in coupling receptor activation to phosphoinositide breakdown. J Biol Chem. 1985 May 10;260(9):5464–5471. [PubMed] [Google Scholar]
  30. Loubatières-Mariani M. M., Chapal J., Alric R., Loubatières A. Studies of the cholinergic receptors involved in the secretion of insulin using isolated perfused rat pancreas. Diabetologia. 1973 Dec;9(6):439–446. doi: 10.1007/BF00461685. [DOI] [PubMed] [Google Scholar]
  31. Malaisse W. J., Brisson G., Malaisse-Lagae F. The stimulus-secretion coupling of glucose-induced insulin release. I. Interaction of epinephrine and alkaline earth cations. J Lab Clin Med. 1970 Dec;76(6):895–902. [PubMed] [Google Scholar]
  32. Malaisse W. J., Carpinelli A. R., Sener A. Stimulus-secretion coupling of glucose-induced insulin release. Timing of early metabolic, ionic, and secretory events. Metabolism. 1981 May;30(5):527–532. doi: 10.1016/0026-0495(81)90191-8. [DOI] [PubMed] [Google Scholar]
  33. Malaisse W. J., Hutton J. C., Sener A., Levy J., Herchuelz A., Devis G., Somers G. Calcium antagonists and islet function: VII. Effect of calcium deprivation. J Membr Biol. 1978 Jan 18;38(3):193–208. doi: 10.1007/BF01871922. [DOI] [PubMed] [Google Scholar]
  34. Mathias P. C., Carpinelli A. R., Billaudel B., Garcia-Morales P., Valverde I., Malaisse W. J. Cholinergic stimulation of ion fluxes in pancreatic islets. Biochem Pharmacol. 1985 Oct 1;34(19):3451–3457. doi: 10.1016/0006-2952(85)90717-8. [DOI] [PubMed] [Google Scholar]
  35. Milner R. D., Hales C. N. The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia. 1967 Mar;3(1):47–49. doi: 10.1007/BF01269910. [DOI] [PubMed] [Google Scholar]
  36. Montague W., Morgan N. G., Rumford G. M., Prince C. A. Effect of glucose on polyphosphoinositide metabolism in isolated rat islets of Langerhans. Biochem J. 1985 Apr 15;227(2):483–489. doi: 10.1042/bj2270483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Morgan N. G., Rumford G. M., Montague W. Studies on the role of inositol trisphosphate in the regulation of insulin secretion from isolated rat islets of Langerhans. Biochem J. 1985 Jun 15;228(3):713–718. doi: 10.1042/bj2280713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Prentki M., Biden T. J., Janjic D., Irvine R. F., Berridge M. J., Wollheim C. B. Rapid mobilization of Ca2+ from rat insulinoma microsomes by inositol-1,4,5-trisphosphate. Nature. 1984 Jun 7;309(5968):562–564. doi: 10.1038/309562a0. [DOI] [PubMed] [Google Scholar]
  39. Putney J. W., Jr, Burgess G. M., Halenda S. P., McKinney J. S., Rubin R. P. Effects of secretagogues on [32P]phosphatidylinositol 4,5-bisphosphate metabolism in the exocrine pancreas. Biochem J. 1983 May 15;212(2):483–488. doi: 10.1042/bj2120483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rana R. S., Mertz R. J., Kowluru A., Dixon J. F., Hokin L. E., MacDonald M. J. Evidence for glucose-responsive and -unresponsive pools of phospholipid in pancreatic islets. J Biol Chem. 1985 Jul 5;260(13):7861–7867. [PubMed] [Google Scholar]
  41. Schibeci A., Schacht J. Action of neomycin on the metabolism of polyphosphoinositides in the guinea pig kidney. Biochem Pharmacol. 1977 Oct 1;26(19):1769–1774. doi: 10.1016/0006-2952(77)90344-6. [DOI] [PubMed] [Google Scholar]
  42. Weiss S. J., McKinney J. S., Putney J. W., Jr Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells. Biochem J. 1982 Sep 15;206(3):555–560. doi: 10.1042/bj2060555. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES