Cell and Tissue Biology

, Volume 9, Issue 2, pp 133–140 | Cite as

Dynamics of proglycogen and macroglycogen in hepatocytes of normal and cirrhotic rat liver at various stages of glycogenesis

  • A. Yu. Chestnova
  • N. N. Bezborodkina
  • N. M. Matyukhina
  • B. N. Kudryavtsev


The content and structure of glycogen in hepatocytes of normal and cirrhotic rat liver were examined at different time intervals after glucose administration to starving animals. We used an original cytofluorimetric method for detection and quantification of proglycogen (PG) and macroglycogen (MG) of isolated hepatocytes. The method is based on the use of reagents of the Schiff type with different spectral characteristics. The content of MG in hepatocytes of control rats was increased by 52% (p < 0.01) as early as after 10 min. The MG content in the cirrhotic liver cells was increased by 43% (p < 0.05) only 20 min after glucose administration to the starving animals. The correlation coefficient between MG content and the total glycogen content at various stages of glycogenesis in rats of both groups was from 0.90 to 0.99 (p < 0.001). Increase in the PG content in hepatocytes of control rats was observed in intervals of 10–30 and 45–75 min. The PG content in cirrhosis was increased only in 60 min after the beginning of glycogenesis, but in 120 min it was 1.5 times higher than the control values (p < 0.001). The correlation coefficients between PG and the total glycogen content in the cells were on average 0.86 (p < 0.001) and 0.77 (p < 0.001) in the control and experimental groups, respectively. Thus, the change in the total glycogen content in hepatocytes of normal and cirrhotic liver are associated mainly with changes in the MG level. The contribution of PG was most significant in normal liver at the beginning of glycogenesis (10–30 min); in cirrhotic liver, at later stages (75–120 min).


proglycogen macroglycogen hepatocytes glycogen synthesis liver cirrhosis glucose 







Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alonso, M.D., Lomako, J., Lomako, W.M., and Whelan, W.J., A new look at the biogenesis of glycogen, FASEB J, 1995, vol. 9, pp. 1126–1137.PubMedGoogle Scholar
  2. Bröjer, J., Proglycogen and macroglycogen in equine skeletal muscle, Doctoral Thesis Swedish University of Agricultural Sciences, Uppsala, 2006.Google Scholar
  3. Brodsky, V.Ya., Rhythm of protein synthesis, J. Theor. Biol., 1975, vol. 55, pp. 167–200.CrossRefGoogle Scholar
  4. Brodsky, V.Ya., Direct cell-cell communication: a new approach derived from recent data on the nature and self-organisation of ultradian (circahoralian) intracellular rhythms, Biol. Rev., 2006, vol. 81, pp. 143–162.CrossRefPubMedGoogle Scholar
  5. Brodsky, V.Ya. and Nechaeva, N.V., Ritm sinteza belka (Rhythm of Protein Synthesis), Moscow: Nauka, 1988.Google Scholar
  6. Devos, P., Baudhuin, P., Van, Hoof, F., and Hers, H.G., The alpha-particulate liver glycogen, Biochem. J., 1983, vol. 209, pp. 159–165.PubMedCentralPubMedGoogle Scholar
  7. Ferrer, J.C., Favre, C., Gomis, R.R., Fernández-Novell, J.M., Garcia-Rocha, M., de la Iglesia, N., Cid, E., and Guinovart, J.J., Control of glycogen deposition, FEBS Lett, 2003, vol. 546, pp. 127–132.CrossRefPubMedGoogle Scholar
  8. Ganesh, S., Agarwala, K.L., Amano, K., Suzuki, T., Delgado-Escueta, A.V., and Yamakawa, K., Regional and developmental expression of epm2a gene and its evolutionary conservation, Biochem. Biophys. Res. Commun., 2001, vol. 283, pp. 1046–1053.CrossRefPubMedGoogle Scholar
  9. Giardina, M.G., Matarazzo, M., and Sacca, L., Kinetic analysis of glycogen synthase and PDC in cirrhotic rat liver and skeletal muscle, Am. J. Physiol., 1994, vol. 267, pp. E900–E906.PubMedGoogle Scholar
  10. Greenberg, C.C., Jurczak, M.J., Danos, A.M., and Brady, M.J., Glycogen branches out: new perspectives on the role of glycogen metabolism in the integration of metabolic pathways, Am. J. Physiol. Endocrinol. Metab., 2006, vol. 291, pp. E1–E8.CrossRefPubMedGoogle Scholar
  11. Judd, C., Lomako, J., Lomako, W.M., Ozdemir, Y., and Whelan, W.J., Proglycogen: an intermediate in glycogen synthesis, FASEB J,, 1992, vol. 6, pp. A1520.Google Scholar
  12. Jurczak, M.J., Danos, A.M., Rehrmann, V.R., and Brady, M.J., The role of protein translocation in the regulation of glycogen metabolism, Cell. Âiochem., 2008, vol. J 104, pp. 435–443.CrossRefGoogle Scholar
  13. Krahenbuhl, S., Weber, F.L.Jr, and Brass, E.P., Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis, Hepatology, 1991, vol. 14, pp. 1189–1195.PubMedGoogle Scholar
  14. Kudryavtseva, M.V., Zavadskaya, E.E., Skorina, A.D., Smirnova, S.A., and Kudryavtsev, B.N., The method of obtaining isolated liver cells of material lifetime puncture biopsies, Lab. Delo, 1983, vol. 9, pp. 21–22.Google Scholar
  15. Kudryavtseva, M.V., Emelyanov, A.V., Sakuta, G.A., Skorina, A.D., Sleptsova, L.A., and Kudryavtsev, B.N., A cytofluorometric study of glycogen contents and its fractions in hepatocytes of patients with different causation of liver cirrhosis, Tsitologiya, 1992, vol. 34, no. 11–12, pp. 100–107.Google Scholar
  16. Kudryavtseva, M.V., Bezborodkina, N.N., Radchenko, V.G., Okovity, S.V., and Kudryavtsev, B.N., Metabolic het-erogeneity of glycogen hepatocytes of patients with liver cirrhosis, Eur. J. Gastroenterol. Hepatol., 2001, vol. 13, pp. 693–697.CrossRefPubMedGoogle Scholar
  17. Kus, I., Colakoglu, N., Pekmez, H., Seckin, D., Ogeturk, M., and Sarsilmaz, M., Protective effects of caffeic acid phenethyl ester (CAPE) on carbon tetrachloride-induced hepatotoxicity in rats, Acta Histochem., 2004, vol. 106, pp. 289–297.CrossRefPubMedGoogle Scholar
  18. Lloyd, D. and Rossi, E.L., Ultradian Rhythms in Life Processes: An Inquiry into Fundamental Principles of Chronobiology and Psychobiology, New York: Springer-Verlag, 1992.CrossRefGoogle Scholar
  19. Mayatepek, E., Hoffmann, B., and Meissner, T., Inborn errors of carbohydrate metabolism, Best Pract. Res. Clin. Gastroenterol., 2010, vol. 24, pp. 607–618.CrossRefPubMedGoogle Scholar
  20. Melendez, R., Melendez-Hevia, E., and Canela, E.I., The fractal structure of glycogen: a clever solution to optimize cell metabolism, J. Biophys., 1999, vol. 77, pp. 1327–1332.CrossRefGoogle Scholar
  21. Petersen, K.F., Krssak, M., Navarro, V., Chandramouli, V., Hundal, R., Schumann, W.C., Landau, B.R., and Shulman, G.I., Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis, Am. J. Physiol., 1999, vol. 276, pp. E529–E535.PubMedGoogle Scholar
  22. Planaguma, A., Claria, J., Miquel, R., Lopez-Parra, M., Titos, E., Masferrer, J.L., Arroyo, V., and Rodes, J., The selective cyclooxygenase-2 inhibitor SC-236 reduces liver fibrosis by mechanisms involving non-parenchymal cell apoptosis and PPARgamma activation, FASEB J., 2005, vol. 19, pp. 1120–1122.PubMedGoogle Scholar
  23. Rozenfeld, E.L. and Popova, I.A., Vrozhdennye narusheniya obmena glikogena (Inborn Errors of Glycogen Metabolism), Moscow: Meditsina, 1989.Google Scholar
  24. Rybicka, K.K., Glycosomes-the organelles of glycogen metabolism, Tiss. Cell., 1996, vol. 28, pp. 253–265.CrossRefGoogle Scholar
  25. Schneiter, P., Gillet, M., Chiolero, R., Jequier, E., and Tappy, L., Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis, Metabolism, 1999, vol. 48, pp. 1260–1266.CrossRefPubMedGoogle Scholar
  26. Shearer, J. and Graham, T.E., New perspectives on the storage and organization of muscle glycogen, Can. J. Appl. Physiol., 2002, vol. 27, pp. 179–203.CrossRefPubMedGoogle Scholar
  27. Shearer, J., Wilson, R.J., Battram, D.S., Richter, E.A., Robinson, D.L., Bakovic, M., and Graham, T.E., Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle, Am. J. Phisiol. Endocrinol. Metab., 2005, vol. 289, pp. E508–E514.CrossRefGoogle Scholar
  28. Sherlock, Sh. and Dooley, J., Liver and Biliary Tract Diseases, Moscow: GEOTAR-media, 2002.Google Scholar
  29. Sullivan, M.A., Vilaplana, F., Cave, R.A., Stapleton, D., Gray-Weale, A.A., and Gilbert, R.G., Nature of α and β particles in glycogen using molecular size distributions, Biomacromolecules, 2010, vol. 11, pp. 1094–1100.CrossRefPubMedGoogle Scholar
  30. Tagliabracci, V.S., Turnbull, J., Wang, W., Girard, J.M., Zhao, X., Skurat, A.V., Delgado-Escueta, A.V., Minassian, B.A., Depaoli-Roach, A.A., and Roach, P.J., Laforin is a glycogen phosphatase, deficiency of which leads to elevated phosphorylation of glycogen in vivo, Proc. Natl. Acad. Sci. U.S.A., 2007, vol. 104, pp. 19262–19266.CrossRefPubMedCentralPubMedGoogle Scholar
  31. Tagliabracci, V.S., Heiss, C., Karthik, C., Contreras, C.J., Glushka, J., Ishihara, M., Azadi, P., Hurley, T.D., DePaoli-Roach, A.A., and Roach, P.J., Phosphate incorporation during glycogen synthesis and lafora, Cell Metab., 2011, vol. 13, pp. 274–282.CrossRefPubMedCentralPubMedGoogle Scholar
  32. Wilson, R.J., Relating glycogenin protein levels and glycogen content post-contraction in human and rodent skeletal muscle, A Thesis for the Degree of Doctor of Philosophy, University of Guelph, 2009.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  • A. Yu. Chestnova
    • 1
  • N. N. Bezborodkina
    • 1
  • N. M. Matyukhina
    • 1
    • 2
  • B. N. Kudryavtsev
    • 1
  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia
  2. 2.Almazov Federal Heart, Blood, and Endocrinology CenterSt. PetersburgRussia

Personalised recommendations