Skip to main content
SpringerLink
Log in

The role of protein kinase C in insulin biosynthesis

  • Originals
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Activation of protein kinase C (PKC) by the phorbol ester 4β-phorbol myristate acetate (4β-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4β-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4β-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an inerease in the amount of preproinsulin mRNA in PKC-depleted islets since Northern blot analysis showed that prolonged exposure to 4β-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of β-cells to glucose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ashcroft SJH, Glucoreceptor mechanisms and the control of insulin release and biosynthesis. Diabetologia 18:5–15, 1980

    Article  PubMed  CAS  Google Scholar 

  2. Itoh N, Okamoto H, Translational control of proinsulin biosynthesis by glucose. Nature 283:100–102, 1980

    Article  PubMed  CAS  Google Scholar 

  3. Bone AJ, Swenne I, Hellerström C, Effects of high glucose concentrations on the insulin biosynthesis of rat pancreatic islets maintained for extended periods in tissue culture. Diabet Metab 7:259–263, 1981

    CAS  Google Scholar 

  4. Prentki M, Matschinsky FM, Ca2+, cAMP and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol Rev 67:1185–1248, 1987

    PubMed  CAS  Google Scholar 

  5. Ashcroft SJH, Bunce J, Lowry M, Hansen SE, Hedeskov CJ, The effects of sugars on (pro)insulin biosynthesis. Biochem J 174:517–526, 1978

    PubMed  CAS  Google Scholar 

  6. Pipeleers DG, Narichal M, Malaisse WJ, The stimulus-secretion coupling of glucose-induced insulin release XIV. Glucose regulation of insular biosynthetic activity. Endocrinology 93:1001–1011, 1973

    Article  PubMed  CAS  Google Scholar 

  7. Welsh M, Weber T, Wrange O, Nielson DA, Matthieu M, Steiner DF, Regulation of insulin gene expression by dexamethasone, Ca2+, and a phorbol ester. Biomed Biochim Acta 47:299–303, 1988

    PubMed  CAS  Google Scholar 

  8. Zawalich WS, Karl RC, Ferendelli JA, Matschinsky FM, Factors governing glucose-induced elevation of cyclic adenosine 3′:5′-monophosphate in pancreatic islets. Diabetologia 11:231–235, 1975

    Article  PubMed  CAS  Google Scholar 

  9. Persaud SJ, Jones PM, Howell SL Glucose-stimulated insulin secretion is not dependent on activation of protein kinase A. Biochem Biophys Res Commun 173:839–839, 1990

    Article  Google Scholar 

  10. Bone AJ, Howell SL, Alterations in regulation of biosynthesis in pregnancy and starvation studied in isolated rat islets of Langerhans. Biochem J 166:501–507, 1977

    PubMed  CAS  Google Scholar 

  11. Peter-Riesch B, Fathi M, Schlegel W, Wollheim CB, Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets. J Clin Invest 81:1154–1161, 1988

    Article  PubMed  CAS  Google Scholar 

  12. Wolf BA, Easom RA, Hughes JH, McDaniel ML, Turk J, Secretagogue-induced diacylglycerol accumulation in isolated pancreatic islets: mass spectrometric characterization of the fatty acyl content indicates multiple mechanisms of generation. Biochemistry 28:4291–4301, 1989

    Article  PubMed  CAS  Google Scholar 

  13. Zawalich WS, Rasmussen H, Control of insulin secretion: a model involving Ca2+, cAMP and diacylglycerol. Mol Cell Endocrinol 70:119–137, 1990

    Article  PubMed  CAS  Google Scholar 

  14. Persaud SJ, Jones PM, Howell SL, The role of protein kinase C in insulin secretion. In: Flatt PR (ed) Nutrient regulation of insulin secretion. Portland Press, London, pp 247–269, 1992

    Google Scholar 

  15. Hammonds P, Schofield PN, Ashcroft SJH Glucose regulates preproinsulin messenger RNA levels in a clonal cell line of Simian virus 40-transformed B-cells. FEBS Lett 213:149–154, 1987

    Article  PubMed  CAS  Google Scholar 

  16. Hammonds P, Schofield PN, Ashcroft SJH, Sutton R, Grey DWR, Regulation and specificity of glucose-stimulated insulin gene expression in human islets of Langerhans. FEBS Lett 223:131–137, 1987

    Article  PubMed  CAS  Google Scholar 

  17. Hii CST, Jones PM, Persaud SJ, Howell SL, A re-assessment of the role of protein kinase C in glucose-stimulated insulin secretion. Biochem J 246:489–493, 1987

    PubMed  CAS  Google Scholar 

  18. Bjaaland T, Jones PM, Howell SL, Role of intracellular mediators in glucagon secretion: studies using intact and electrically permeabilised rat islets of Langerhans. J Mol Endocrinol 1:171–178, 1988

    Article  PubMed  CAS  Google Scholar 

  19. Gey GO, Gey MK, The maintenance of human normal cells in continuous culture. Preliminary report: cultivation of mesoblastic tumors and normal cells and notes on methods of cultivation. Am J Cancer 27:45–76, 1936

    Google Scholar 

  20. Persaud SJ, Jones PM, Sugden D, Howell SL, The role of protein kinase C in cholinergic stimulation of insulin secretion from rat islets of Langerhans. Biochem J 264:753–758, 1989

    PubMed  CAS  Google Scholar 

  21. Persaud SJ, Jones PM, Sugden D, Howell SL, Translocation of protein kinase C in rats islets of Langerhans: effects of a phorbol ester, carbachol and glucose. FEBS Lett 245:80–84, 1989

    Article  PubMed  CAS  Google Scholar 

  22. Slee DJ, Jones PM, Howell SL, Proinsulin processing in electrically permeabilised rat islets of Langerhans. J Mol Endocrinol 5:275–280, 1990

    Article  PubMed  CAS  Google Scholar 

  23. Jones PM, Salmon DMW, Howell SL, Protein phosphorylation in electrically permeabilised islets of Langerhans: effects of Ca2+, cyclic AMP, a phorbol ester and noradrenaline. Biochem J 254:397–403, 1988

    PubMed  CAS  Google Scholar 

  24. Chomczynski P, Sacchi N, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159, 1987

    Article  PubMed  CAS  Google Scholar 

  25. Nishizuka Y The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334:661–665, 1988

    Article  PubMed  CAS  Google Scholar 

  26. Lappin D, Whaley K, The role of ion channels and protein kinase C in the stimulation of complement protein synthesis. J Clin Lab Immunol 24:57–62, 1987

    PubMed  CAS  Google Scholar 

  27. Houchi H, Nakanishi A, Uddin MM, Ohuchi T, Oka M, Phorbol ester stimulates catecholamine synthesis in isolated bovine adrenal medullary cells. FEBS Lett 188:205–208, 1985

    Article  PubMed  CAS  Google Scholar 

  28. Ramsdell JS, Pettit GR, Tasjian AH, Three activators of protein kinase C, bryostatins, dioleins and phorbol esters, show differing specificities of action on GH4 pituitary cells. J Biol Chem 261:17073–17080, 1986

    PubMed  CAS  Google Scholar 

  29. Stojikovic SS, Chang JP, Ngo D, Catt KJ, Evidence for a role of protein kinase C in luteinizing hormone synthesis and secretion: impaired responses to gonadotrophin-releasing hormone in protein kinase C-depleted pituitary cells J Biol Chem 263:17307–17311, 1988

    Google Scholar 

  30. Kley N, Multiple regulation of proenkephalin gene expression by protein kinase C. J Biol Chem 263:2003–2008, 1988

    PubMed  CAS  Google Scholar 

  31. Yamato E, Ikegami H, Tahara Y, Cha T, Yoneda H, Noma Y, Shima K, Ogihara T, Role of protein kinase C in the regulation of glucagon gene expression by arginine. Biochem Biophys Res Commun 171:898–904, 1990

    Article  PubMed  CAS  Google Scholar 

  32. Ito A, Saito N, Taniguchi H, Chiba T, Kikkawa U, Saitoh Y, Tanaka C, Localization of βII subspecies of protein kinase C in β-cells. Diabetes 38:1005–1011, 1989

    Article  PubMed  CAS  Google Scholar 

  33. Onoda K, Hagiwara M, Hachiya T, Usuda N, Nagata T, Hidaka H, Different expression of protein kinase C isozymes in pancreatic islet cells. Endocrinology 126:1235–1240, 1990

    Article  PubMed  CAS  Google Scholar 

  34. Itoh N, Sei T, Nose K, Okamoto H, Glucose stimulation of the proinsulin synthesis in isolated pancreatic islets without increasing amount of proinsulin mRNA. FEBS Lett 93:343–347, 1978

    Article  PubMed  CAS  Google Scholar 

  35. Welsh M, Scherberg N, Gilmore R, Steiner DF, Translational control of insulin biosynthesis: evidence for regulation of elongation, initiation and signal-recognition particle-mediated translational arrest by glucose. Biochem J 235:459–467, 1986

    PubMed  CAS  Google Scholar 

  36. Welsh M, Nielsen DA, MacKrell AJ, Steiner DF, Control of insulin gene expression in pancreatic β-cells and in an insulinproducing cell line, RIN-m5F cells. II. Regulation of insulin mRNA stability. J Biol Chem 260:13590–13594, 1985

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, University of Brighton, Brighton, Sussex, UK

    D. J. Gwilliam

  2. Biomedical Sciences Division, King's College London, London, UK

    P. M. Jones, S. J. Persaud & S. L. Howell

Authors
  1. D. J. Gwilliam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. M. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. J. Persaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. L. Howell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gwilliam, D.J., Jones, P.M., Persaud, S.J. et al. The role of protein kinase C in insulin biosynthesis. Acta Diabetol 30, 99–104 (1993). https://doi.org/10.1007/BF00578222

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00578222

Key words

Search

Navigation