Home LiteratureArticle Details
PMID: 2407236 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phorbol-ester-induced down-regulation of protein kinase C in mouse pancreatic islets. Potentiation of phase 1 and inhibition of phase 2 of glucose-induced insulin secretion.

The Biochemical journal ·Vol. 265 ·No. 3 ·1990-02-01 ·Pages 777-87

Thams P, Capito K, Hedeskov CJ, Kofod H

Abstract

The influence of down-regulation of protein kinase C on glucose-induced insulin secretion was studied. A 22-24 h exposure of mouse pancreatic islets to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 0.16 microM) in RPMI 1640 culture medium (8.3 mM-glucose, 0.43 mM-Ca2+) abolished TPA (0.16 microM)-induced insulin secretion and led to a potentiation of phase 1 and a decrease in phase 2 of glucose-induced insulin secretion. Thus, although the total insulin release during 40 min of perfusion with glucose (16.7 mM) (45-85 min) was unaffected, the percentage released during phase 1 (45-55 min) was increased from 12.9 +/- 1.5 (4)% in controls to 35.8 +/- 3.9 (4)% in TPA-treated islets (P less than 0.01), and the percentage released during phase 2 (65-85 min) was decreased from 63.2 +/- 3.9 (4)% to 35.3 +/- 1.4 (4)% (P less than 0.005). In contrast, TPA exposure in TCM 199 medium (5.5 mM-glucose, 1.26 mM-Ca2+) caused a total abolition of both phases 1 and 2 of glucose-induced secretion. However, inclusion of the alpha 2-adrenergic agonists adrenaline (10 microM) or clonidine (10 microM), or lowering of the Ca2+ concentration in TCM 199 during down-regulation, preserved and potentiated phase 1 of glucose-induced secretion. Furthermore, perifusion of islets in the presence of staurosporine (1 microM), an inhibitor of protein kinase C, potentiated phase 1 and inhibited phase 2 of glucose-induced secretion. In addition, down-regulation of protein kinase C potentiated phase 1 and inhibited phase 2 of carbamoylcholine (100 microM)-induced insulin secretion at 3.3 mM-glucose, and abolished the potentiating effect of carbamoylcholine (100 microM) at 16.7 mM-glucose. These results substantiate a role for protein kinase C in insulin secretion, and suggest that protein kinase C inhibits phase 1 and stimulates phase 2 of both glucose-induced and carbamoylcholine-induced insulin secretion.

MeSH Terms
Alkaloids/pharmacology Animals Carbachol/pharmacology Down-Regulation Glucose/pharmacology Insulin/metabolism Insulin Secretion Islets of Langerhans/drug effects,enzymology Male Mice Phosphorylation Protein Kinase C/metabolism Staurosporine Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Alkaloids Insulin Carbachol Protein Kinase C Staurosporine Glucose Tetradecanoylphorbol Acetate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Thams P
Department of Biochemistry A, University of Copenhagen, Denmark.
Capito K
Hedeskov C J
Kofod H
References (37)
37 references, click to expand
  1. Somatostatin- and epinephrine-induced modifications of 45Ca++ fluxes and insulin release in rat pancreatic islets maintained in tissue culture.
    J Clin Invest. 1977 Nov;60(5):1165-73 PMID: 332717
  2. Phosphoinositide hydrolysis and insulin release from isolated perifused rat islets. Studies with glucose.
    Diabetes. 1988 Sep;37(9):1294-300 PMID: 2842212
  3. Cellular mechanisms of insulin release. Effects of retinol on insulin release and islet ultrastructure.
    Diabetes. 1979 Aug;28(8):754-61 PMID: 376383
  4. Insulinotropic effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in rat pancreatic islets.
    Cancer Res. 1980 Oct;40(10):3827-31 PMID: 6254641
  5. Ventral and dorsal areas of rat pancreas: islet hormone content and secretion.
    Am J Physiol. 1981 Apr;240(4):E422-7 PMID: 6111929
  6. Alpha 2-adrenergic inhibition of insulin secretion via interference with cyclic AMP generation in rat pancreatic islets.
    Mol Pharmacol. 1982 May;21(3):648-53 PMID: 6125877
  7. The molecular heterogeneity of protein kinase C and its implications for cellular regulation.
    Nature. 1988 Aug 25;334(6184):661-5 PMID: 3045562
  8. Stimulation by glucose of cyclic AMP accumulation in mouse pancreatic islets is mediated by protein kinase C.
    Biochem J. 1988 Jul 1;253(1):229-34 PMID: 2844166
  9. Retinal inhibits TPA activated, calcium-dependent, phospholipid-dependent protein kinase ("C" kinase).
    Biochem Biophys Res Commun. 1983 Aug 12;114(3):1194-9 PMID: 6615513
  10. L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase.
    Am J Physiol. 1983 Oct;245(4):E338-46 PMID: 6194691
  11. Insulin secretion: combined effects of phorbol ester and A23187.
    Biochem Biophys Res Commun. 1983 Dec 16;117(2):448-55 PMID: 6229253
  12. Insulin release independent of a rise in cytosolic free Ca2+ by forskolin and phorbol ester.
    FEBS Lett. 1985 Apr 22;183(2):430-2 PMID: 2985438
  13. Effect of glucose on polyphosphoinositide metabolism in isolated rat islets of Langerhans.
    Biochem J. 1985 Apr 15;227(2):483-9 PMID: 2988501
  14. 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 PMID: 2409943
  15. Intracellular Ca2+ mobilization by arachidonic acid. Comparison with myo-inositol 1,4,5-trisphosphate in isolated pancreatic islets.
    J Biol Chem. 1986 Mar 15;261(8):3501-11 PMID: 3081507
  16. Enhancement of glucagon secretion from isolated rat islets of Langerhans by phorbol 12-myristate 13-acetate.
    Biochem J. 1986 Jan 1;233(1):287-9 PMID: 3513761
  17. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase.
    Biochem Biophys Res Commun. 1986 Mar 13;135(2):397-402 PMID: 3457562
  18. Differences in adrenergic recognition by pancreatic A and B cells.
    Science. 1986 May 16;232(4752):875-7 PMID: 2871625
  19. Stimulation of insulin release by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate in the clonal cell line RINm5F despite a lowering of the free cytoplasmic Ca2+ concentration.
    Biochim Biophys Acta. 1986 Jul 11;887(2):236-41 PMID: 3521749
  20. Glucose-induced phospholipid-dependent protein phosphorylation in neonatal rat islets.
    Arch Biochem Biophys. 1986 Aug 1;248(2):562-9 PMID: 3527065
  21. Protein kinase C phosphorylates human platelet inositol trisphosphate 5'-phosphomonoesterase, increasing the phosphatase activity.
    Cell. 1986 Sep 12;46(6):951-8 PMID: 3019558
  22. A role for calcium in the breakdown of inositol phospholipids in intact and digitonin-permeabilized pancreatic islets.
    Biochem J. 1986 Sep 15;238(3):773-9 PMID: 3541917
  23. Potentiators of insulin secretion modulate Ca2+ sensitivity in rat pancreatic islets.
    Mol Cell Endocrinol. 1987 Apr;50(3):231-6 PMID: 3552784
  24. Catecholamine inhibition of Ca2+-induced insulin secretion from electrically permeabilised islets of Langerhans.
    FEBS Lett. 1987 Jul 13;219(1):139-44 PMID: 3036595
  25. Alpha 2-adrenoceptor stimulation affects total glucose utilization in isolated islets of Langerhans.
    Mol Pharmacol. 1987 Aug;32(1):241-8 PMID: 2441240
  26. Inositol trisphosphate and diacylglycerol: two interacting second messengers.
    Annu Rev Biochem. 1987;56:159-93 PMID: 3304132
  27. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion.
    Physiol Rev. 1987 Oct;67(4):1185-248 PMID: 2825225
  28. Distinct mechanisms for two amplification systems of insulin release.
    Biochem J. 1987 Sep 1;246(2):393-9 PMID: 2825637
  29. A re-assessment of the role of protein kinase C in glucose-stimulated insulin secretion.
    Biochem J. 1987 Sep 1;246(2):489-93 PMID: 3318809
  30. Perspectives in diabetes. Is protein kinase C required for physiologic insulin release?
    Diabetes. 1988 Jan;37(1):3-7 PMID: 3121416
  31. Regulation of erythrocyte Ca2+ pump activity by protein kinase C.
    J Biol Chem. 1988 Feb 15;263(5):2195-202 PMID: 2963001
  32. Synergism between vasopressin and phorbol esters in stimulation of insulin secretion and phosphatidylcholine metabolism in RIN insulinoma cells.
    Biochem Biophys Res Commun. 1988 Mar 15;151(2):717-24 PMID: 2831902
  33. Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets.
    J Clin Invest. 1988 Apr;81(4):1154-61 PMID: 2832445
  34. Mechanisms involved in intracellular calcium mobilization in isolated rat islets of Langerhans.
    Biochem J. 1987 Jun 15;244(3):669-74 PMID: 3128266
  35. Effects of a phorbol ester and clomiphene on protein phosphorylation and insulin secretion in rat pancreatic islets.
    Biochem J. 1988 Feb 1;249(3):825-30 PMID: 3281655
  36. GTP-dependent inhibition of insulin secretion by epinephrine in permeabilized RINm5F cells. Lack of correlation between insulin secretion and cyclic AMP levels.
    J Biol Chem. 1988 Jun 25;263(18):8615-20 PMID: 2837460
  37. A comparison of the effects of glucose and acetylcholine on insulin release and intermediary metabolism in rat pancreatic islets.
    J Biol Chem. 1979 May 25;254(10):3921-9 PMID: 220227
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2650777
Published
1990-02-01
Pages
777-87
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1133701
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2650777 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2