Skip to main content
SpringerLink
Log in

Anabolic Response to Cell Swelling in the Liver

  • Chapter
Contributions of Physiology to the Understanding of Diabetes

Abstract

The study of the mechanisms responsible for the stimulation of liver glycogen synthesis by some amino acids has allowed us to discover that cell swelling was mediating not only a stimulation of glycogen synthesis but also lipogenesis. This led to the general idea that cell swelling triggers an anabolic response of the cell. This proposal was confirmed by the observation of its effect on protein synthesis/breakdown. This chapter briefly describes our wanderings through this field and summarizes our findings and the observations made by others. It also deals with the more recent concern with the anabolic signalling triggered by cell swelling.

At best, we are slowly reaching the stage at which we are aware of how little we know

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Seglen PO (1974) Autoregulation of glycolysis, respiration, gluconeogenesis and glycogen synthesis in isolated parenchymal rat liver cells under aerobic and anaerobic conditions. Biochim Biophys Acta 338: 317–336

    CAS  Google Scholar 

  2. Hue L, Bontemps F, Hers HG (1975) The effect of glucose and of potassium ions on the interconversion of the two forms of glycogen Phosphorylase and of glycogen synthetase in isolated rat liver preparations. Biochem J 152: 105–114

    PubMed  CAS  Google Scholar 

  3. Katz J, Wals PA, Golden S, Rognstad R (1975) Recycling of glucose by rat hepatocytes. Eur J Biochem 60: 91–101

    Article  PubMed  CAS  Google Scholar 

  4. Stalmans W, van de Werve G (1981) Regulation of glycogen metabolism by insulin. In: Hue L, van de Werve G (eds) Short-term regulation of liver metabolism, Elsevier, Amsterdam, pp 119–138

    Google Scholar 

  5. Katz J, Golden S, Wals PA (1976) Stimulation of hepatic glycogen synthesis by amino acids. Proc Natl Acad Sci USA 73: 3433–3437

    Article  PubMed  CAS  Google Scholar 

  6. Lavoinne A, Baquet A, Hue L (1987) Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes. Biochem J 248: 429–437

    PubMed  CAS  Google Scholar 

  7. Baquet A, Lavoinne A, Hue L (1991) Comparison of the effects of various amino acids on glycogen synthesis, lipogenesis and ketogenesis in isolated rat hepatocytes. Biochem J 273: 57–62

    PubMed  CAS  Google Scholar 

  8. Okajima F, Katz J (1979) Effects of mercaptopicolinic acid and of transaminase inhibitors on glycogen synthesis by rat hepatocytes. Biochem Biophys Res Commun 87: 155–162

    Article  PubMed  CAS  Google Scholar 

  9. Rognstad R (1986) Effects of amino acid analogs and amino acid mixtures on glycogen synthesis in rat hepatocytes. Biochem Arch 2: 185–190

    CAS  Google Scholar 

  10. Bode AM, Nordlie RC (1993) Reciprocal effects of proline and glutamine on glycogenesis from glucose and ureagenesis in isolated, perfused rat liver. J Biol Chem 268: 16298–16301

    PubMed  CAS  Google Scholar 

  11. Rognstad R (1985) Possible role for carbamyl phosphate in the control of liver glycogen synthesis. Biochem Biophys Res Commun 130: 229–233

    Article  PubMed  CAS  Google Scholar 

  12. Gustafson L, Romp N, van Woerkom GM, Meijer AJ (1994) Carbamoyl phosphate and ureagenesis are not involved in amino-acid-stimulated glycogenesis. Eur J Biochem 223: 553–556

    Article  PubMed  CAS  Google Scholar 

  13. Solanki K, Moser U, Nyfeler F, Walter P (1982) Possible correlation between the stimulation of glycogen synthesis by some amino acids and the synthesis of purines in hepatocytes from starved rats. Experientia 38:732

    Google Scholar 

  14. Carabaza A, Ricart MD, Mor A, Guinovart JJ, Ciudad CJ (1990) Role of AMP on the activation of glycogen synthase and Phosphorylase by adenosine, fructose and glutamine in rat hepatocytes. J Biol Chem 265: 2724–2732

    PubMed  CAS  Google Scholar 

  15. Bakker-Grunwald T (1983) Potassium permeability and volume control in isolated rat hepatocytes. Biochim Biophys Acta 731: 239–242

    Article  PubMed  CAS  Google Scholar 

  16. Kristensen LØ, Folke M (1984) Volume-regulatory K+ efflux during concentrative uptake of alanine in isolated rat hepatocytes. Biochem J 221: 265–268

    PubMed  CAS  Google Scholar 

  17. Roach PJ (1990) Control of glycogen synthase by hierarchal protein phosphorylation. FASEB J 4: 2961–2968

    PubMed  CAS  Google Scholar 

  18. Hardie DG, Carling D, Sim ATR (1989) The ATP-activated protein kinase: a multisubstrate regulator of lipid metabolism. Trends Biochem Sci 14: 20–23

    Article  CAS  Google Scholar 

  19. Davies SP, Sim ATR, Hardie DG (1990) Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase. Eur J Biochem 187: 183–190

    Article  PubMed  CAS  Google Scholar 

  20. Hardie DG (1992) Regulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase. Biochim Biophys Acta 1123: 231–238

    PubMed  CAS  Google Scholar 

  21. Baquet A, Hue L, Meijer AJ, van Woerkom GM, Plomp PJAM (1990) Swelling of rat hepatocytes stimulates glycogen synthesis. J Biol Chem 265: 955–959

    PubMed  CAS  Google Scholar 

  22. Baquet A, Maisin L, Hue L (1991) Swelling of rat hepatocytes activates acetyl-CoA carboxylase in parallel to glycogen synthase. Biochem J 278: 887–890

    PubMed  CAS  Google Scholar 

  23. Häussinger D, Lang F (1991) Cell volume in the regulation of hepatic function: a mechanism for metabolic control. Biochim Biophys Acta 1071: 331–350

    PubMed  Google Scholar 

  24. Häussinger D (1995) Regulation of metabolism by changes in cellular hydration. Clin Nut 14:4–12

    Article  Google Scholar 

  25. Häussinger D, Schliess F (1995) Cell volume and hepatocellular function. J Hepatol 22: 94–100

    Article  PubMed  Google Scholar 

  26. Al-Habori M, Peak M, Thomas TH, Agius L (1992) The role of cell swelling in the stimulation of glycogen synthesis by insulin. Biochem J 282: 789–796

    PubMed  CAS  Google Scholar 

  27. Peak M, Al-Habori M, Agius L (1992) Regulation of glycogen synthesis and glycolysis by insulin, pH and cell volume. Interactions between swelling and alkalinization in mediating the effects of insulin. Biochem J 282: 797–805

    PubMed  CAS  Google Scholar 

  28. Stoll B, Gerok W, Lang F, Häussinger D (1992) Liver cell volume and protein synthesis. Biochem J 287:217–222

    PubMed  CAS  Google Scholar 

  29. Guzman M, Velasco G, Castro J, Zammit VA (1994) Inhibition of carnitine palmitoyltransferase I by hepatocyte swelling. FEBS Lett 344: 239–241

    Article  PubMed  CAS  Google Scholar 

  30. Meijer AJ, Gustafson LA, Luiken JJ, Blommaart PJ, Caro LH, van Woerkom GM, Spronk C, Boon L (1993) Cell swelling and the sensitivity of autophagic proteolysis to inhibition by amino acids in isolated rat hepatocytes. Eur J Biochem 215: 449–454

    Article  PubMed  CAS  Google Scholar 

  31. Häussinger D, Hallbrucker C, Saha N, Lang F, Gerok W (1992) Cell volume and bile acid excretion. Biochem J 288: 681–689

    PubMed  Google Scholar 

  32. Bode AM, Kilberg MS (1991) Amino acid-dependent increase in hepatic system N activity is linked to cell swelling. J Biol Chem 266: 7376–7381

    PubMed  CAS  Google Scholar 

  33. Hallbrucker C, Lang F, Gerok W, Häussinger D (1992) Cell swelling increases bile flow and taurocholate excretion into bile in isolated perfused rat liver. Biochem J 281: 593–595

    PubMed  CAS  Google Scholar 

  34. Tohyama Y, Kameji T, Hayashi S (1991) Mechanisms of dramatic fluctuations of ornithine decarboxylase activity upon tonicity changes in primary cultured rat hepatocytes. Eur J Biochem 202: 1327–1331

    Article  PubMed  CAS  Google Scholar 

  35. Finkenzeller G, Newsome WP, Lang F, Häussinger D (1994) Increase of c-jun mRNA upon hypoosmotic cell swelling of rat hepatoma cells. FEBS Lett 340: 163–166

    Article  PubMed  CAS  Google Scholar 

  36. Theodoropoulos PA, Stournaras C, Stoll B, Markogiannakis E, Lang F, Gravanis A, Häussinger D (1992) Hepatocyte swelling leads to rapid decrease of the G-/total actin ratio and increases actin mRNA levels. FEBS Lett 311: 241–245

    Article  PubMed  CAS  Google Scholar 

  37. Häussinger D, Stoll B, vom Dahl S (1994) Effect of hepatocyte swelling on microtube stability and tubulin mRNA levels. Biochem Cell Biol 72: 12–19

    Article  PubMed  Google Scholar 

  38. Newsome WP, Warskulat U, Noe B, Wettstein M, Stoll B, Gerok W, Häussinger D (1994) Modulation of phosphoenolpyruvate carboxykinase mRNA levels by the hepatocellular hydration state. Biochem J 304: 555–560

    PubMed  CAS  Google Scholar 

  39. Wettstein M, vom Dahl S, Lang F, Gerok W, Häussinger D (1990) Cell volume regulatory responses of isolated perfused rat liver. Biol Chem Hoppe Seyler 371: 493–501

    Article  PubMed  CAS  Google Scholar 

  40. Krebs HA (1980) Glutamine metabolism in the animal body. In: Mora J, Palacios R (eds) Glutamine: metabolism, enzymology and regulation. Academic, New York, pp 319–329

    Google Scholar 

  41. Meister A (1980) Catalytic mechanism of glutamine synthetase; overview of glutamine metabolism. In: Mora J, Palacios R (eds) Glutamine: metabolism, enzymology and regulation. Academic, New York, pp 1–40

    Google Scholar 

  42. Kovacevic Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32: 326–333

    PubMed  CAS  Google Scholar 

  43. Windmueller HG (1980) Enterohepatic aspects of glutamine metabolism. In: Mora J, Palacios R (eds) Glutamine: metabolism, enzymology and regulation. Academic, New York, pp 235–257

    Google Scholar 

  44. Zielke HR, Zielke CI, Ozand PT (1984) Glutamine: a major energy source for cultured mammalian cells. Fed Proc 43: 121–125

    PubMed  CAS  Google Scholar 

  45. Häussinger D (1983) Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intercellular glutamine cycle during ureagenesis in rat liver. Eur J Biochem 133:269–275

    Article  PubMed  Google Scholar 

  46. Häussinger D (1986) Regulation of hepatic ammonia metabolism: the intercellular glutamine cycle. Adv Enzyme Regul 25: 159–180

    Article  PubMed  Google Scholar 

  47. Gaussin V, Baquet A, Hue L (1992) Cell shrinkage follows rather than mediates the short-term effects of glucagon on carbohydrate metabolism. Biochem J 287: 17–20

    PubMed  CAS  Google Scholar 

  48. Hoffmann EK, Simonsen LO (1989) Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol Rev 69: 315–382

    PubMed  CAS  Google Scholar 

  49. Bontemps F, Hue L, Hers HG (1978) Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone. Biochem J 174: 603–611

    PubMed  CAS  Google Scholar 

  50. Lang F, Stehle T, Häussinger D (1989) Water, K+, H+, lactate and glucose fluxes during cell volume regulation in perfused rat liver. Pflugers Arch 413: 209–216

    Article  PubMed  CAS  Google Scholar 

  51. Gleeson D, Corasanti JG, Boyer JL (1990) Effects of osmotic stresses on isolated rat hepatocytes. II. Modulation of intracellular pH. Am J Physiol 258: G299–G307

    PubMed  CAS  Google Scholar 

  52. Baquet A, Meijer A J, Hue L (1991) Hepatocytes swelling increases inositol 1,4,5-trisphosphate, calcium and cyclic AMP concentration but antagonizes Phosphorylase activation by Ca3+-dependent hormones. FEBS Lett 278: 103–106

    Article  PubMed  CAS  Google Scholar 

  53. Watson PA (1989) Accumulation of cAMP and calcium in S49 mouse lymphoma cells following hypoosmotic swelling. J Biol Chem 264: 14735–14740

    PubMed  CAS  Google Scholar 

  54. Hazama A, Okada Y (1990) Involvement of Ca2+-induced Ca2+ release in the volume regulation of human epithelial cells exposed to a hypotonic medium. Biochem Biophys Res Commun 167: 287–293

    Article  PubMed  CAS  Google Scholar 

  55. vom Dahl S, Hallbrucker C, Lang F, Häussinger D (1991) Role of eicosanoids, inositol phosphates and extracellular Ca2+ in cell volume regulation of rat liver. Eur J Biochem 198: 73–83

    Article  Google Scholar 

  56. Meijer AJ, Baquet A, Gustafson L, van Woerkom G, Hue L (1992) Mechanism of activation of liver glycogen synthase by swelling. J Biol Chem 267: 5823–5828

    PubMed  CAS  Google Scholar 

  57. Plomp PJAM, Boon L, Caro LHP, van Woerkom GM, Meijer AJ (1990) Stimulation of glycogen synthesis in hepatocytes by added amino acids is related to the total intracellular content of amino acids. Eur J Biochem 191: 237–243

    Article  PubMed  CAS  Google Scholar 

  58. Baquet A, Gaussin V, Bollen M, Stalmans W, Hue L (1993) Mechanism of activation of liver acetyl-CoA carboxylase by cell swelling. Eur J Biochem 217: 1083–1089

    Article  PubMed  CAS  Google Scholar 

  59. Gaussin V, Hue L, Stalmans W, Bollen M (1995) The activation of hepatic acetyl-CoA carboxylase by glutamate and Mg2+ is mediated by protein phosphatase-2A. Biochem J 316: 217–224

    Google Scholar 

  60. Cohen P (1989) The structure and regulation of protein phosphatases. Annu Rev Biochem 58:453–508

    Article  PubMed  CAS  Google Scholar 

  61. Denton RM, Tavaré JM (1995) Does mitogen-activated protein kinase have a role in insulin action? Eur J Biochem 227: 597–611

    Article  PubMed  CAS  Google Scholar 

  62. Agius L, Peak M, Beresford G, Al-Habori M, Thomas TH (1994) The role of ion content and cell volume in insulin action. Biochem Soc Trans 22: 516–522

    PubMed  CAS  Google Scholar 

  63. Blommaart EFC, Luiken JJFP, Blommaart PJE, van Woerkom GM, Meijer A J (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem 270: 2320–2326

    Article  PubMed  CAS  Google Scholar 

  64. Krause K, Rider MH, Hue L (1996) Protein kinase signalling pathway triggered by cell swelling and involved in the activation of glycogen synthesis and acetyl-CoA carboxylase in isolated rat hepatocytes. J Biol Chem 271: 16668–16673

    Article  PubMed  CAS  Google Scholar 

  65. Dent P, Lavoinne A, Nakielny S, Caudwell FB, Watt P, Cohen P (1990) The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle. Nature 348: 302–308

    Article  PubMed  CAS  Google Scholar 

  66. Lavoinne A, Erikson E, Maller JL, Price DL, Avruch J, Cohen P (1991) Purification and characterization of the insulin-stimulated protein kinase from rabbit skeletal muscle; close similarity to S6 kinase II. Eur J Biochem 199: 723–728

    Article  PubMed  CAS  Google Scholar 

  67. Cross DAE, Alessi DR, Vandenheede JR, McDowell HE, Hundal HS, Cohen P (1994) The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin, but not by rapamycin: evidence that wortmannin blocks activation of the mitogen-activated protein kinase pathway in L6 cells between Ras and Raf. Biochem J 303: 21–26

    PubMed  CAS  Google Scholar 

  68. Tilly BC, van den Berghe N, Tertoolen LGJ, Edixhoven MJ, de Jonge HR (1993) Protein tyrosine phosphorylation is involved in osmoregulation of ionic conductances. J Biol Chem 268: 19919–19922

    PubMed  CAS  Google Scholar 

  69. Han J, Lee J-D, Bibbs L, Ulevitch RJ (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265: 808–811

    Article  PubMed  CAS  Google Scholar 

  70. Brewster JL, de Valoir T, Dwyer ND, Winter E, Gustin MC (1993) An osmosensing signal transduction pathway in yeast. Science 259: 1760–1763

    Article  PubMed  CAS  Google Scholar 

  71. Maeda T, Wurgler-Murphy SM, Saito H (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369: 242–245

    Article  PubMed  CAS  Google Scholar 

  72. Galcheva-Gargova Z, Dérijard B, Wu I-H, Davis RJ (1994) An osmosensing signal transduction pathway in mammalian cells. Science 265: 806–808

    Article  PubMed  CAS  Google Scholar 

  73. Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamzares A, Zamanillo D, Hunt T, Nebreda AR (1995) A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78: 1027–1037

    Article  Google Scholar 

  74. Swanson RV, Alex LA, Simon MI (1994) Histidine and aspartate phosphorylation: two-component systems and the limits of homology. TIBS 19: 485–490

    PubMed  CAS  Google Scholar 

  75. Cano E, Mahadevan LC (1995) Parallel signal processing among mammalian MAPKs. Trends Biochem Sci 20: 117–122

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. L. Hue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Gaussin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Krause
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fondation pour Recherches Médicales Faculté de Médecine, Université de Genève, 64, Avenue dela Roseraie, 1211, Genève 4, Switzerland

    Gaston R. Zahnd

  2. Division de Biochimie clinique et de Diabétologie expérimentale, Centre Médical Universitaire, 1211, Genève 4, Switzerland

    Claes B. Wollheim

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hue, L., Gaussin, V., Krause, U. (1997). Anabolic Response to Cell Swelling in the Liver. In: Zahnd, G.R., Wollheim, C.B. (eds) Contributions of Physiology to the Understanding of Diabetes. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60475-1_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60475-1_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64422-1

  • Online ISBN: 978-3-642-60475-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation