Skip to main content

Advertisement

SpringerLink
Log in

Lithium Induces Glycogen Accumulation in Salivary Glands of the Rat

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Lithium is administered for the treatment of mood and bipolar disorder. The aim of this study was to verify whether treatment with different concentrations of lithium may affect the glycogen metabolism in the salivary glands of the rats when compared with the liver. Mobilization of glycogen in salivary glands is important for the process of secretion. Two sets of experiments were carried out, that is, in the first, the rats received drinking water supplemented with LiCl (38,25 and 12 mM of LiCl for 15 days) and the second experiment was carried out by intraperitoneal injection of LiCl solution (12 mg/kg and 45 mg LiCl/kg body weight) for 3 days. The active form of glycogen phosphorylase was not affected by treatment with LiCl considering the two experiments. The active form of glycogen synthase presented higher activity in the submandibular glands of rats treated with 25 and 38 mM LiCl and in the liver, with 25 mM LiCl. Glycogen level was higher than that of control in the submandibular glands of rats receiving 38 and 12 mM LiCl, in the parotid of rats receiving 25 and 38 mM, and in the liver of rats receiving 12 mM LiCl. The absolute value of glycogen for the submandibular treated with 25 mM LiCl, and the liver treated with 38 mM LiCl, was higher than the control value, although not statistically significant for these tissues. No statistically significant difference was found in the submandibular and parotid salivary glands for protein concentration when comparing experimental and control groups. We concluded that LiCl administered to rats influences the metabolism of glycogen in salivary glands.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Schrauzer GN (2002) Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 21(1):14–21

    Article  PubMed  CAS  Google Scholar 

  2. Baldessarini RJ, Tondo L (2000) Does lithium treatment still work? Evidence of stable responses over three decades. Arch Gen Psychiatry 57(2):187–190

    Article  PubMed  CAS  Google Scholar 

  3. Nivoli AM, Murru A, Goikolea JM, Crespo JM, Montes JM, Gonzalez-Pinto A, Garcia-Portilla P, Bobes J, Saiz-Ruiz J, Vieta E (2012) New treatment guidelines for acute bipolar mania: a critical review. J Affect Disord 140(2):125–141

    Article  PubMed  Google Scholar 

  4. Szabadi E, Tavernor S (1999) Hypo- and hypersalivation induced by psychoactive drugs—incidence, mechanisms and therapeutic implications. CNS Drugs 11(6):449–466

    Article  CAS  Google Scholar 

  5. Popovic J, Krsljak E, Grbovic L, Stojic D (2005) The effects of acute and chronic lithium treatment on rat submandibular salivation. Oral Dis 11(2):100–103

    Article  PubMed  CAS  Google Scholar 

  6. Markitziu A, Shani J, Avni J (1988) Salivary gland function in patients on chronic lithium treatment. Oral Surg Oral Med Oral Pathol 66(5):551–557

    Article  PubMed  CAS  Google Scholar 

  7. Dehpour AR, Abdollahi M, Alghasi H (1995) Effects of lithium on rat parotid and submandibulary gland functions. Gen Pharmacol 26(4):851–854

    Article  PubMed  CAS  Google Scholar 

  8. Nicolau J, Sassaki KT (1983) Metabolism of carbohydrate in vitro of the submandibular salivary glands (SMG) from mice injected with isoproterenol. Gen Pharmacol 14(6):705–708

    Article  PubMed  CAS  Google Scholar 

  9. Nicolau J, de Souza DN, Martins HR (1992) Pilocarpine-induced increases in the activity of 6-phosphofructo-2-kinase and the fructose-2,6-bisphosphate content of rat salivary glands. Arch Oral Biol 37(6):483–487

    Article  PubMed  CAS  Google Scholar 

  10. Herman G, Rossignol B (1975) Regulation of protein secretion and metabolism in rat salivary glands. Effects of norepinephrine and carbachol on the glycogenolysis in submaxillary glands. Eur J Biochem 55(1):105–110

    Article  PubMed  CAS  Google Scholar 

  11. Garrett JR, Thomopoulos GN, Zhang XS, Hartley R (1994) The fate of glycogen in granular tubule cells of rat submandibular glands during secretory events. Arch Oral Biol 39(5):449–452

    Article  PubMed  CAS  Google Scholar 

  12. Souza AD, da Silva GSS, Velez BS, Santoro ABM, Montero-Lomeli M (2010) Glycogen synthesis in brain and astrocytes is inhibited by chronic lithium treatment. Neurosci Lett 482(2):128–132

    Article  CAS  Google Scholar 

  13. Rodriguez-Gil JE, Fernandez-Novell JM, Barbera A, Guinovart JJ (2000) Lithium's effects on rat liver glucose metabolism in vivo. Arch Biochem Biophys 375(2):377–384

    Article  PubMed  CAS  Google Scholar 

  14. Haugaard ES, Mickel RA, Haugaard N (1974) Actions of lithium ions and insulin on glucose-utilization, glycogen-synthesis and glycogen synthase in isolated rat diaphragm. Biochem Pharmacol 23(12):1675–1685

    Article  PubMed  CAS  Google Scholar 

  15. Cheng K, Creacy S, Larner J (1983) ‘Insulin-like’ effects of lithium ion on isolated rat adipocytes. II. Specific activation of glycogen synthase. Mol Cell Biochem 56(2):183–189

    PubMed  CAS  Google Scholar 

  16. Bosch F, Gomez-Foix AM, Arino J, Guinovart JJ (1986) Effects of lithium ions on glycogen synthase and phosphorylase in rat hepatocytes. J Biol Chem 261(36):16927–16931

    PubMed  CAS  Google Scholar 

  17. Nordenberg J, Kaplansky M, Beery E, Klein S, Beitner R (1982) Effects of lithium on the activities of phosphofructokinase and phosphoglucomutase and on glucose-1,6-diphosphate levels in rat muscles, brain and liver. Biochem Pharmacol 31(6):1025–1031

    Article  PubMed  CAS  Google Scholar 

  18. Csutora P, Karsai A, Nagy T, Vas B, Kovacs GL, Rideg O, Bogner P, Miseta A (2006) Lithium induces phosphoglucomutase activity in various tissues of rats and in bipolar patients. Int J Neuropsychopharmacol 9(5):613–619

    Article  PubMed  CAS  Google Scholar 

  19. Rose IA, Warms JVB (1980) Lithium action on glucose-uptake in brain—role of glucose-1,6-P2 as a regulator of hexokinase. Biochem Biophys Res Commun 92(3):1030–1036

    Article  PubMed  CAS  Google Scholar 

  20. Freland L, Beaulieu JM (2012) Inhibition of GSK3 by lithium, from single molecules to signaling networks. Front Mol Neurosci 5:14

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Stambolic V, Ruel L, Woodgett JR (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol 6(12):1664–1668

    Article  PubMed  CAS  Google Scholar 

  22. Nciri R, Allagui MS, Bourogaa E, Saoudi M, Murat JC, Croute F, Elfeki A (2012) Lipid peroxidation, antioxidant activities and stress protein (HSP72/73, GRP94) expression in kidney and liver of rats under lithium treatment. J Physiol Biochem 68(1):11–1823

    Article  PubMed  CAS  Google Scholar 

  23. Tandon A, Dhawan DK, Nagpaul JP (1998) Effect of lithium on hepatic lipid peroxidation and antioxidative enzymes under different dietary protein regimens. J Appl Toxicol 18(3):187–190

    Article  PubMed  CAS  Google Scholar 

  24. Bendz H, Aurell M (1999) Drug-induced diabetes insipidus: incidence, prevention and management. Drug Saf Int J Med Toxicol Drug Exp 21(6):449–456

    Article  CAS  Google Scholar 

  25. Forrest Jr JN, Cohen AD, Torretti J, Himmelhoch JM, Epstein FH (1974) On the mechanism of lithium-induced diabetes insipidus in man and the rat. J Clin Invest 53(4):1115–1123

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Livingstone C, Rampes H (2006) Lithium: a review of its metabolic adverse effects. J Psychopharmacol 20(3):347–355

    Article  PubMed  Google Scholar 

  27. Garfinkel PE, Ezrin C, Stancer HC (1973) Hypothyroidism and hyperparathyroidism associated with lithium. Lancet 2(7824):331–332

    Article  PubMed  CAS  Google Scholar 

  28. Rifai MA, Moles JK, Harrington DP (2001) Lithium-induced hypercalcemia and parathyroid dysfunction. Psychosomatics 42(4):359–361

    Article  PubMed  CAS  Google Scholar 

  29. Eduardo Cde P, Simoes A, de Freitas PM, Arana-Chavez VE, Nicolau J, Gentil V (2013) Dentin decalcification during lithium treatment: case report. Spec Care Dentist 33(2):91–95

    Article  PubMed  Google Scholar 

  30. Nicolau J, de Matos JA, de Souza DN, Neves LB, Lopes AC (2005) Altered glycogen metabolism in the submandibular and parotid salivary glands of rats with streptozotocin-induced diabetes. J Oral Sci 47(2):111–116

    Article  PubMed  CAS  Google Scholar 

  31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    PubMed  CAS  Google Scholar 

  32. Alonso MD, Lomako J, Lomako WM, Whelan WJ (1995) A new look at the biogenesis of glycogen. FASEB J Off Publ Fed Am Soc Exp Biol 9(12):1126–1137

    CAS  Google Scholar 

  33. Bollen M, Keppens S, Stalmans W (1998) Specific features of glycogen metabolism in the liver. Biochem J 336(Pt 1):19–31

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Cohen P (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296(5858):613–620

    Article  PubMed  CAS  Google Scholar 

  35. Roach PJ (1981) Glycogen synthase and glycogen synthase kinases. Curr Top Cell Regul 20:45–105

    Article  PubMed  CAS  Google Scholar 

  36. Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS (2012) Glycogen and its metabolism: some new developments and old themes. Biochem J 441:763–787

    Article  PubMed  CAS  Google Scholar 

  37. Charest R, Prpic V, Exton JH, Blackmore PF (1985) Stimulation of inositol trisphosphate formation in hepatocytes by vasopressin, adrenaline and angiotensin II and its relationship to changes in cytosolic free Ca2+. Biochem J 227(1):79–90

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Tabata I, Schluter J, Gulve EA, Holloszy JO (1994) Lithium increases susceptibility of muscle glucose transport to stimulation by various agents. Diabetes 43(7):903–907

    Article  PubMed  CAS  Google Scholar 

  39. Bosch F, Rodriguezgil JE, Hatzoglou M, Gomezfoix AM, Hanson RW (1992) Lithium inhibits hepatic gluconeogenesis and phosphoenolpyruvate carboxykinase gene expression. J Biol Chem 267(5):2888–2893

    PubMed  CAS  Google Scholar 

  40. Newgard CB, Hwang PK, Fletterick RJ (1989) The family of glycogen phosphorylases—structure and function. Crit Rev Biochem Mol 24(1):69–99

    Article  CAS  Google Scholar 

  41. Browner MF, Fletterick RJ (1992) Phosphorylase—a biological transducer. Trends Biochem Sci 17(2):66–71

    Article  PubMed  CAS  Google Scholar 

  42. Nyfeler F, Fasel P, Walter P (1981) Short-term stimulation of net glycogen production by insulin in rat hepatocytes. Biochim Biophys Acta 675(1):17–23

    Article  PubMed  CAS  Google Scholar 

  43. Roach PJ (1990) Control of glycogen synthase by hierarchal protein phosphorylation. FASEB J Off Publ Fed Am Soc Exp Biol 4(12):2961–2968

    CAS  Google Scholar 

  44. Stalmans W, Bollen M, Mvumbi L (1987) Control of glycogen synthesis in health and disease. Diabetes Metab Rev 3(1):127–161

    Article  PubMed  CAS  Google Scholar 

  45. Jope RS (2003) Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol Sci 24(9):441–443

    Article  PubMed  CAS  Google Scholar 

  46. Jurysta C, Nicaise C, Giroix MH, Cetik S, Malaisse WJ, Sener A (2013) Comparison of GLUT1, GLUT2, GLUT4 and SGLT1 mRNA expression in the salivary glands and six other organs of control, streptozotocin-induced and Goto-Kakizaki diabetic rats. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 31(1):37–43

    Article  CAS  Google Scholar 

  47. Nicolau J, Ganzerla E, de Souza DN (2003) Glycogen content and activities of enzymes involved in the carbohydrate metabolism of the salivary glands of rats during postnatal development. Arch Oral Biol 48(2):101–109

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Biomateriais e Biologia Oral, Faculdade de Odontologia, Universidade de São Paulo (USP), Av. Prof. Lineu Prestes, São Paulo, SP, 2227, Brazil

    D. N. Souza, F. N. Nogueira, A. Simões & J. Nicolau

  2. Departamento Ortodontia e Odontopediatria, Faculdade de Odontologia, Universidade de São Paulo (USP), Av. Prof. Lineu Prestes, São Paulo, SP, 2227, Brazil

    F. M. Mendes

Authors
  1. D. N. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. M. Mendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. N. Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Simões
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Nicolau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Nicolau.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Souza, D.N., Mendes, F.M., Nogueira, F.N. et al. Lithium Induces Glycogen Accumulation in Salivary Glands of the Rat. Biol Trace Elem Res 169, 271–278 (2016). https://doi.org/10.1007/s12011-015-0434-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0434-0

Keywords

Search

Navigation