Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1987 Sep 1;246(2):489–493. doi: 10.1042/bj2460489

A re-assessment of the role of protein kinase C in glucose-stimulated insulin secretion.

C S Hii 1, P M Jones 1, S J Persaud 1, S L Howell 1
PMCID: PMC1148300  PMID: 3318809

Abstract

Isolated rat islets of Langerhans which had been pretreated with 200 nM-phorbol 12-myristate 13-acetate (PMA) for 20-24 h, a treatment reported in other cell types to deplete cells of protein kinase C activity, were found not to contain detectable Ca2+/phospholipid-dependent protein kinase activity. These islets did not secrete insulin in response to a subsequent exposure to PMA (0.1 or 1 microM) during a 30 min incubation, although insulin secretion could be stimulated by 20 mM-glucose, a response which was enhanced by 20 microM-forskolin. PMA-pretreated islets that had been permeabilized by high-voltage discharge showed unimpaired secretory responses to an increase in Ca2+ concentration, cyclic AMP and forskolin. These results suggest that (i) pretreatment of islets with tumour-promoting phorbol esters may be a useful means of investigating the role of protein kinase C in stimulus-secretion coupling in the pancreatic beta-cell and (ii) protein kinase C may not play an essential role in glucose-induced insulin secretion.

Full text

PDF
490

Selected References

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

  1. 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]
  2. 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]
  3. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  4. Gainer H. S., Murray A. W. Diacylglycerol inhibits gap junctional communication in cultured epidermal cells: evidence for a role of protein kinase C. Biochem Biophys Res Commun. 1985 Feb 15;126(3):1109–1113. doi: 10.1016/0006-291x(85)90300-6. [DOI] [PubMed] [Google Scholar]
  5. Harrison D. E., Ashcroft S. J., Christie M. R., Lord J. M. Protein phosphorylation in the pancreatic B-cell. Experientia. 1984 Oct 15;40(10):1075–1084. doi: 10.1007/BF01971454. [DOI] [PubMed] [Google Scholar]
  6. Henquin J. C. The interplay between cyclic AMP and ions in the stimulus-secretion coupling in pancreatic B-cells. Arch Int Physiol Biochim. 1985 May;93(1):37–48. doi: 10.3109/13813458509104514. [DOI] [PubMed] [Google Scholar]
  7. Hii C. S., Stutchfield J., Howell S. L. Enhancement of glucagon secretion from isolated rat islets of Langerhans by phorbol 12-myristate 13-acetate. Biochem J. 1986 Jan 1;233(1):287–289. doi: 10.1042/bj2330287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Howell S. L., Taylor K. W. Potassium ions and the secretion of insulin by islets of Langerhans incubated in vitro. Biochem J. 1968 Jun;108(1):17–24. doi: 10.1042/bj1080017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hubinont C. J., Best L., Sener A., Malaisse W. J. Activation of protein kinase C by a tumor-promoting phorbol ester in pancreatic islets. FEBS Lett. 1984 May 21;170(2):247–253. doi: 10.1016/0014-5793(84)81322-8. [DOI] [PubMed] [Google Scholar]
  10. Hutton J. C., Peshavaria M., Brocklehurst K. W. Phorbol ester stimulation of insulin release and secretory-granule protein phosphorylation in a transplantable rat insulinoma. Biochem J. 1984 Dec 1;224(2):483–490. doi: 10.1042/bj2240483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jones P. M., Stutchfield J., Howell S. L. Effects of Ca2+ and a phorbol ester on insulin secretion from islets of Langerhans permeabilised by high-voltage discharge. FEBS Lett. 1985 Oct 21;191(1):102–106. doi: 10.1016/0014-5793(85)81002-4. [DOI] [PubMed] [Google Scholar]
  12. Katakami Y., Nakao Y., Matsui T., Koizumi T., Kaibuchi K., Takai Y., Fujita T. Possible involvement of protein kinase C in interleukin-1 production by mouse peritoneal macrophages. Biochem Biophys Res Commun. 1986 Mar 13;135(2):355–362. doi: 10.1016/0006-291x(86)90002-1. [DOI] [PubMed] [Google Scholar]
  13. Kitano T., Go M., Kikkawa U., Nishizuka Y. Assay and purification of protein kinase C. Methods Enzymol. 1986;124:349–352. doi: 10.1016/0076-6879(86)24026-4. [DOI] [PubMed] [Google Scholar]
  14. Klip A., Ramlal T. Protein kinase C is not required for insulin stimulation of hexose uptake in muscle cells in culture. Biochem J. 1987 Feb 15;242(1):131–136. doi: 10.1042/bj2420131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kojima I., Lippes H., Kojima K., Rasmussen H. Aldosterone secretion: effect of phorbol ester and A23187. Biochem Biophys Res Commun. 1983 Oct 31;116(2):555–562. doi: 10.1016/0006-291x(83)90559-4. [DOI] [PubMed] [Google Scholar]
  16. Lord J. M., Ashcroft S. J. Identification and characterization of Ca2+-phospholipid-dependent protein kinase in rat islets and hamster beta-cells. Biochem J. 1984 Apr 15;219(2):547–551. doi: 10.1042/bj2190547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Malaisse W. J., Sener A., Herchuelz A., Carpinelli A. R., Poloczek P., Winand J., Castagna M. Insulinotropic effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in rat pancreatic islets. Cancer Res. 1980 Oct;40(10):3827–3831. [PubMed] [Google Scholar]
  18. Mazzei G. J., Katoh N., Kuo J. F. Polymyxin B is a more selective inhibitor for phospholipid-sensitive Ca2+-dependent protein kinase than for calmodulin-sensitive Ca2+-dependent protein kinase. Biochem Biophys Res Commun. 1982 Dec 31;109(4):1129–1133. doi: 10.1016/0006-291x(82)91894-0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  21. Pasti G., Lacal J. C., Warren B. S., Aaronson S. A., Blumberg P. M. Loss of mouse fibroblast cell response to phorbol esters restored by microinjected protein kinase C. 1986 Nov 27-Dec 3Nature. 324(6095):375–377. doi: 10.1038/324375a0. [DOI] [PubMed] [Google Scholar]
  22. Qi D. F., Schatzman R. C., Mazzei G. J., Turner R. S., Raynor R. L., Liao S., Kuo J. F. Polyamines inhibit phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases. Biochem J. 1983 Aug 1;213(2):281–288. doi: 10.1042/bj2130281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
  24. Salacinski P. R., McLean C., Sykes J. E., Clement-Jones V. V., Lowry P. J. Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent, 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl glycoluril (Iodogen). Anal Biochem. 1981 Oct;117(1):136–146. doi: 10.1016/0003-2697(81)90703-x. [DOI] [PubMed] [Google Scholar]
  25. Sharp G. W. The adenylate cyclase-cyclic AMP system in islets of Langerhans and its role in the control of insulin release. Diabetologia. 1979 May;16(5):287–296. doi: 10.1007/BF01223617. [DOI] [PubMed] [Google Scholar]
  26. Stutchfield J., Jones P. M., Howell S. L. The effects of polymyxin B, a protein kinase C inhibitor, on insulin secretion from intact and permeabilized islets of Langerhans. Biochem Biophys Res Commun. 1986 May 14;136(3):1001–1006. doi: 10.1016/0006-291x(86)90432-8. [DOI] [PubMed] [Google Scholar]
  27. Summers S. T., Cronin M. J. Phorbol esters enhance basal and stimulated adenylate cyclase activity in a pituitary cell line. Biochem Biophys Res Commun. 1986 Feb 26;135(1):276–281. doi: 10.1016/0006-291x(86)90973-3. [DOI] [PubMed] [Google Scholar]
  28. Thams P., Capito K., Hedeskov C. J. An inhibitory role for polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets. Biochem J. 1986 Jul 1;237(1):131–138. doi: 10.1042/bj2370131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Virji M. A., Steffes M. W., Estensen R. D. Phorbol myristate acetate: effect of a tumor promoter on insulin release from isolated rat islets of Langerhans. Endocrinology. 1978 Mar;102(3):706–711. doi: 10.1210/endo-102-3-706. [DOI] [PubMed] [Google Scholar]
  30. Watanabe Y., Horn F., Bauer S., Jakobs K. H. Protein kinase C interferes with Ni-mediated inhibition of human platelet adenylate cyclase. FEBS Lett. 1985 Nov 11;192(1):23–27. doi: 10.1016/0014-5793(85)80035-1. [DOI] [PubMed] [Google Scholar]
  31. Wise B. C., Glass D. B., Chou C. H., Raynor R. L., Katoh N., Schatzman R. C., Turner R. S., Kibler R. F., Kuo J. F. Phospholipid-sensitive Ca2+-dependent protein kinase from heart. II. Substrate specificity and inhibition by various agents. J Biol Chem. 1982 Jul 25;257(14):8489–8495. [PubMed] [Google Scholar]
  32. 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]

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

RESOURCES