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The Role of Phospholipid Metabolism in Insulin Action

  • Robert V. Farese
  • Denise R. Cooper

Abstract

There are two major mechanisms whereby hormones and other agonists alter phospholipid metabolism and generate intracellular signaling substances in their respective target tissues, viz., phospholipase activation and phospholipid synthesis. The most widely popularized mechanism involves the activation of a specific phospholipase C which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2).1 This hydrolysis generates inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which, respectively, mobilize Ca++ from intracellular stores and activate protein kinase C2 and other possibly related kinases. This hydrolytic mechanism is probably operative in the action of most agonists which operate via cell surface receptors and use Ca++ as a major intracellular signaling substance. In addition to PIP2 hydrolysis, other types of phospholipase C may be activated, causing the hydrolysis of phosphatidylcholine (PC),3 phosphatidylinositol (PI) or a PI-glucosamine complex (PI-glycan).4 While it is clear that cell surface receptors are coupled to the PIP2 phospholipase C through GTP-binding proteins (which may or may not be inhibited by pertussis toxin), little is known about the mechanisms whereby receptors activate other forms of phospholipase C.

Keywords

Glucose Transport Insulin Action Insulin Treatment Phosphatidic Acid Phorbol Ester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    M. J. Berridge, and R. F. Irvine, Inositol trisphosphate, a novel second messenger in cellular signal transduction Nature 312: 315 (1984).Google Scholar
  2. 2.
    Y. Nishizuka, Studies and perspectives of protein kinase C, Science 233: 305 (1986).PubMedCrossRefGoogle Scholar
  3. 3.
    J. M. Besterman, V. Duronio, and P. Cuatrecasas, Rapid formation of diacyl- glycerol from phosphatidylcholine: a pathway for generation of a second messenger, Proc. Natl. Acad. Sci. USA 83: 6785 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    A. R. Saltiel, J. A. Fox, P. Sherline, and P. Cuatrecasas, Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase, Science 233: 967 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    R. V. Farese, De novo phospholipid synthesis as an intracellular mediator system, in: “Phospholipids and Cellular Regulation,” J. Kuo, ed., CRC Press, Boca Raton, FL (1985).Google Scholar
  6. 6.
    R. V. Farese, R. E. Larson, and M. A. Sabir, Insulin acutely increases phospholipids in the phosphatidate-inositide cycle in rat adipose tissue, J. Biol. Chem. 257: 4042 (1982).PubMedGoogle Scholar
  7. 7.
    R. V. Farese, D. E. Barnes, J. S. Davis, M. L. Standaert, and R. J. Pollet, Effects of insulin and protein synthesis inhibitors on phospholipid metabolism, diacylglycerol levels, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes, J. Biol. Chem. 259: 7094 (1984).PubMedGoogle Scholar
  8. 8.
    R. V. Farese, J. S. Davis, D. E. Barnes, M. L. Standaert, J. S. Babischkin, R. Hock, N. K. Rosic, and R. J. Pollet, The de novo phospholipid effect of insulin is associated with increases in diacylglycerol, but not inositol phosphates or cytosolic Ca2+, Biochem. J. 231: 269 (1985).Google Scholar
  9. 9.
    R. V. Farese, M. A. Sabir, and R. E. Larson, Comparison of changes in inositide and noninositide phospholipids during acute and prolonged adrenocorticotropic hormone treatment in vivo, Biochem. 21: 3318 (1982).CrossRefGoogle Scholar
  10. 10.
    R. V. Farese, M. A. Sabir, and R. E. Larson, Effects of adrenocorticotropin and cycloheximide on adrenal diglyceride kinase, Biochem. 20: 6047 (1981).CrossRefGoogle Scholar
  11. 11.
    S. R. Pennington, and B. R. Martin, Insulin-stimulated phosphoinositide metabolism in isolated fat cells, J. Biol. Chem. 260: 11039 (1985).PubMedGoogle Scholar
  12. 12.
    M. I. Gonzatti-Haces, and J. A. Traugh, Cat+-independent activation of protease-activated kinase II by phospholipids/diolein and comparison with Caz+/phospholipid-dependent protein kinase, J. Biol. Chem. 261: 15266 (1986).PubMedGoogle Scholar
  13. 13.
    S. Pontremoli, E. Melloni, M. Michetti, F. Salamino, B. Sparatore, O. Sacco, and B. L. Horecker, Differential mechanisms of translocation of protein kinase C to plasma membrane in activated human neutrophils, Biochem. Bionhvs. Res. Commun. 136: 228 (1986).CrossRefGoogle Scholar
  14. 14.
    A. R. Saltiel, P. Sherline, and J. A. Fox, Insulin-stimulated diacylglycerol production results from the hydrolysis of a novel phosphatidylinositol glycan, J. Biol. Chem. 262: 1116 (1987).PubMedGoogle Scholar
  15. 15.
    J. Mato, and L. Jarett, personal communication.Google Scholar
  16. 16.
    B. R. Ganong, C. R. Loomis, Y. A. Hannun, and R. M. Bell, Specificity and mechanism of protein kinase C activation by sn-1,2-diacylglycerols, Proc. Natl. Acad. Sci. USA 83: 1184 (1986).PubMedCrossRefGoogle Scholar
  17. 17.
    R. V. Farese, T. S. Konda, J. S. Davis, M. L. Standaert, R. J. Pollet, and D. R. Cooper, Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis, accepted for publication, Science (1987).Google Scholar
  18. 18.
    R. V. Farese, J. Y. Kuo, J. S. Babischkin, and J. S. Davis, Insulin provokes a transient activation of phospholipase C in the rat epididymal fat pad, J. Biol. Chem. 261: 8589 (1986).PubMedGoogle Scholar
  19. 19.
    T. W. Honeyman, personal communication.Google Scholar
  20. 20.
    D. R. Cooper, H. Hernandez, J. Y. Kuo, and R. V. Farese, Insulin increases de novo synthesis of phosphatidic acid and diacylglycerol and protein kinase C activity in rat hepatocytes, submitted for publication.Google Scholar
  21. 21.
    D. R. Cooper, T. S. Konda, M. L. Standaert, J. S. Davis, R. J. Pollet, and R. V. Farese, Insulin increases membrane and cytosolic protein kinase C activity in BC3H-1 myocytes, in press, J. Biol. Chem. (1987).Google Scholar
  22. 22.
    D. H. Spach, R. A. Nemenoff, and P. J. Blackshear, Protein phosphorylation and protein kinase activities in BC3H-1 myocytes, J. Biol. Chem. 261: 12750 (1986).PubMedGoogle Scholar
  23. 23.
    D. R. Cooper, C. M. Galaretta, L. F. Fanjul, L. Mojsilovic, M. L. Standaert, R. J. Pollet, and R. V. Farese, Insulin but not phorbol ester treatment increases phosphorylation of vinculin by protein kinase C in BC3H-1 myocytes, accepted for publication, FEBS Lett. (1987).Google Scholar
  24. 24.
    C. Cochet, C. Souvignet, M. Keramidas, and E. M. Chambaz, Altered catalytic properties of protein kinase C in phorbol ester treated cells, • Biochem. Biophvs. Res, Commun, 134: 10031 (1986).Google Scholar
  25. 25.
    D. Tabarini, J. Heinrich, and O. M. Rosen, Activation of S6 kinase activity in 3T3–L1 cells by insulin and phorbol ester, Proc. Natl. Acad. Sci. USA 82: 4369 (1985).PubMedCrossRefGoogle Scholar
  26. 26.
    R. V. Farese, M. L. Standaert, D. E. Barnes, J. S. Davis, and R. J. Pollet, Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes, Endocrinology 116: 2650 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    G. Cherqui, M. Caron, D. Wicek, O. Lascols, J. Capeau, and J. Picard, Insulin stimulation of glucose metabolism in rat adipocytes: possible implication of protein kinase C, Endocrinology 118: 1759 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    D. Kirsch, B. Obermaier, and H. U. Haring, Phorbol esters enhance basal D-glucose transport but inhibit insulin stimulation of D-glucose transport and insulin binding in isolated rat adipocytes, Biochim. Biophvs. Acta 128: 824 (1985).Google Scholar
  29. 29.
    J. S. Ramsdell, G. R. Pettit, and A. H. Tashjian, Jr., Three activators of protein kinase C, bryostatins, dioleins, and phorbol esters, show differing specificities of action of GH4 pituitary cells, J. Biol. Chem. 261: 17073 (1986).PubMedGoogle Scholar
  30. 30.
    Z. Kiss, and Y. Luo, Phorbol ester and 1,2-diolein are not fully equivalent activators of protein kinase C in respect to phosphorylation of membrane proteins in vitro, FEBS Lett. 198: 203 (1986).PubMedCrossRefGoogle Scholar
  31. 31.
    O. Shinohara, M. Knecht, and K. J. Catt, Differential actions of phorbol ester and diacylglycerol on inhibition of granulosa cell maturation, Biochem. Biophvs. Res. Commun. 133: 468 (1985).CrossRefGoogle Scholar
  32. 32.
    L. Coussens, P. J. Parker, L. Rhee, T. L. Yang-Feng, E. Chen, M. D. Waterfield, U. Francke, and A. Ullrich, Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signalling pathways, Science 233: 859 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    K.-P. Huang, H. Nakabayashi, and F. L. Huang, Isozymic forms of rat brain Cat+-activated and phospholipid-dependent protein kinase, Proc. Natl. Acad. Sci. USA 83: 8535 (1986).PubMedCrossRefGoogle Scholar
  34. 34.
    F. Vara, and E. Rozengurt, Stimulation of Na+/H+ antiport activity by epidermal growth factor and insulin occurs without activation of protein kinase C, Biochem. Biophvs. Res. Commun. 130: 646 (1985).CrossRefGoogle Scholar
  35. 35.
    K. Kitagawa, H. Nishino, and A. Iwashima, Effect of protein kinase C activation and Ca2+ mobilization on hexose transport in Swiss 3T3 cells, Biochim. Biophvs. Acta 887: 100 (1986).CrossRefGoogle Scholar
  36. 36.
    P. J. Blackshear, R. A. Nemenoff, J. B. Hovis, D. L. Halsey, D. J. Stumpo, and J.-K. Huang, Insulin action in normal and protein kinase C-deficient rat hepatoma cells. Effects on protein phosphorylation, protein kinase activities, and ornithine decarboxylase activities and messenger ribonucleic acid levels, Mol. Endo. 1: 44 (1987).Google Scholar
  37. 37.
    E. Karnieli, M. J. Zarnnowski, P. J. Hissin, I. A. Simpson, L. B. Salans, and S. W. Cushman, Insulin-stimulated translocation of glucose transport systems in the isolated rat adipose cell, J. Biol. Chem. 256: 4772 (1981).PubMedGoogle Scholar
  38. 38.
    K. Suzuki, and T. Kono, Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site, Proc. Natl. Acad. Sci. USA, 77: 2542 (1980).PubMedCrossRefGoogle Scholar
  39. 39.
    J. Larner, G. Galasko, K. Cheng, A. A. DePaoli-Roach, L. Huang, P. Daggy, and J. Kellogg, Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation, Science 206: 1408 (1979).PubMedCrossRefGoogle Scholar
  40. 40.
    L. Jarett, E. H. A. Wong, S. L. Macaulay, and J. A. Smith, Insulin mediators from rat skeletal muscle have differential effects on insulin-sensitive pathways of intact adipocytes, Science 227: 533 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Robert V. Farese
    • 1
  • Denise R. Cooper
    • 1
  1. 1.University of South Florida College of Medicine and J. A. Haley Veterans HospitalTampaUSA

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