Skip to main content

Advertisement

Log in

Na+-Glucose Cotransporter SGLT1 Protein in Salivary Glands: Potential Involvement in the Diabetes-Induced Decrease in Salivary Flow

  • Published:
Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

Oral health complications in diabetes include decreased salivary secretion. The SLC5A1 gene encodes the Na+-glucose cotransporter SGLT1 protein, which not only transports glucose, but also acts as a water channel. Since SLC5A1 expression is altered in kidneys of diabetic subjects, we hypothesize that it could also be altered in salivary glands, contributing to diabetic dysfunction. The present study shows a diabetes-induced decrease (p < 0.001) in salivary secretion, which was accompanied by enhanced (p < 0.05) SGLT1 mRNA expression in parotid (50%) and submandibular (30%) glands. Immunohistochemical analysis of parotid gland of diabetic rats revealed that SGLT1 protein expression increased in the luminal membrane of ductal cells, which can stimulate water reabsorption from primary saliva. Furthermore, SGLT1 protein was reduced in myoepithelial cells of the parotid from diabetic animals, and that, by reducing cellular contractile activity, might also be related to reduced salivary flux. Six-day insulin-treated diabetic rats reversed all alterations. In conclusion, diabetes increases SLC5A1 gene expression in salivary glands, increasing the SGLT1 protein content in the luminal membrane of ductal cells, which, by increasing water reabsorption, might explain the diabetes-induced decrease in salivary secretion.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aydin S (2007) A comparison of ghrelin, glucose, alpha-amylase and protein levels in saliva from diabetics. J Biochem Mol Biol 40:29–35

    PubMed  CAS  Google Scholar 

  • Belazi MA, Glli-Tsinopoulou A, Drakoulakos D, Fleva A, Papanayiotou PH (1998) Salivary alterations in insulin-dependent diabetes mellitus. Int J Paediatr Dent 8(1):29–33

    Article  PubMed  CAS  Google Scholar 

  • Ben-Aryeh H, Cohen M, Kanter Y, Szargel R, Laufer D (1988) Salivary composition in diabetic patients. J Diabet Complicat 2(2):96–99

    Article  CAS  Google Scholar 

  • Campbell MJ (1965) Glucose in the saliva of the non-diabetic and the diabetic patient. Arch Oral Biol 10:197–205

    Article  PubMed  CAS  Google Scholar 

  • Carda C, Mosquera-Lloreda N, Salom L, Gomez de Ferraris ME, Peydró A (2006) Structural and functional salivary disorders in type 2 diabetic patients. Med Oral Patol Oral Cir Bucal 11:309–314

    Google Scholar 

  • Cecanho R, Anaya M, Renzi A, Menani JV, Luca LAD Jr (1999) Sympathetic mediation of salivation induced by intracerebroventricular pilocarpine in rats. J Auton Nerv Syst 76:9–14

    Article  PubMed  CAS  Google Scholar 

  • Cohen DW, Friedman LA, Shapiro J, Kyle GC, Franklin S (1970) Diabetes mellitus and periodontal disease: two year longitudinal observations. Part I. J Periodontol 41:709–712

    PubMed  CAS  Google Scholar 

  • Conner S, Iranpour B, Mills J, Rochester NY (1970) Alteration in parotid salivary flow in diabetes mellitus. Oral Surg Oral Med Oral Pathol 30(1):55–59

    Article  PubMed  CAS  Google Scholar 

  • Elfeber K, Stümpel F, Gouboulev V, Mattig S, Deussen A, Kaissling B, Koepsell H (2004) Na+-D-glucose cotransporter in muscle capillaries increases glucose permeability. Biochem Biophys Res Commun 314:301–305

    Article  PubMed  CAS  Google Scholar 

  • Forbat LN, Collins RE, Maskell GK, Sönksen PH (1981) Glucose concentrations in parotid fluid and venous blood of patients attending a diabetic clinic. J R Soc Med 74(10):725–728

    PubMed  CAS  Google Scholar 

  • Freitas HS, Anhê GF, Melo KF, Okamoto MM, Oliveira-Souza M, Bordin S, Machado UF (2008) Na(+)-glucose transporter–2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1 alpha expression and activity. Endocrinology 149:717–724

    Article  PubMed  CAS  Google Scholar 

  • Hand AR, Weiss RE (1984) Effects of streptozotocin-induced diabetes on the rat parotid gland. Lab Invest 51(4):429–440

    PubMed  CAS  Google Scholar 

  • Hediger MA, Kanai Y, You G, Nussberger S (1995) Mammalian ion-coupled solute transporters. J Physiol 482:7–17

    Google Scholar 

  • Hintao J, Teanpaisan R, Chongsuvivatwong V, Ratarasan C, Dahlen G (2007) The microbiological profiles of saliva, supragingival and subgingival plaque and dental caries in adults with and without type 2 diabetes mellitus. Oral Microbiol Immunol 22(3):175–181

    Article  PubMed  CAS  Google Scholar 

  • Karjalainen KM, Knuuttila ML, Käär ML (1996) Salivary factors in children and adolescents with insulin-dependent diabetes mellitus. Pediatr Dent 18(4):306–311

    PubMed  CAS  Google Scholar 

  • Kerr M, Lee A, Wang PL, Purushotham KR, Chegini N, Yamamoto H, Humphreys-Beher MG (1995) Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type1 diabetes mellitus. Biochem Pharmacol 49(10):1521–1531

    Article  PubMed  CAS  Google Scholar 

  • Klip A, Tsakiridis T, Marette A, Ortz PA (1994) Regulation of expression of glucose transporters by glucose: a review of studies in vivo and in cell cultures. FASEB J 8:43–53

    PubMed  CAS  Google Scholar 

  • Lin CC, Sun SS, Kao A, Lee CC (2002) Impaired salivary function in patients with noninsulin-dependent diabetes mellitus with xerostomia. J Diabetes Complicat 16:176–179

    Article  PubMed  Google Scholar 

  • Loo DDF, Wright EM, Zeuthen T (2002) Water pumps. J Physiol 42:53–60

    Article  Google Scholar 

  • Mangos JA, Maragos N, McSherry NR (1973) Micropuncture and microperfusion study of glucose excretion in rat parotid saliva. Am J Physiol 224(6):1260–1264

    PubMed  CAS  Google Scholar 

  • Murrah VA (1985) Diabetes mellitus and oral manifestations: a review. J. Oral Pathol 14:271–281

    Article  PubMed  CAS  Google Scholar 

  • Newrick PG, Bowman C, Green D, O’Brien IAD, Porter SR, Scully C, Corrall RJM (1991) Parotid salivary secretion in diabetic autonomic neuropathy. J Diabetes Complicat 5:35–37

    Article  CAS  Google Scholar 

  • Renzi A, Colombari E, Matos Filho TR, Silveira JEN, Saad WA, Camargo LAA, De Luca Jr LA, Deróbio JG, Menani JV (1993) Involvement of the central nervous system in the salivary secretion induced by pilocarpine in rats. J Dent Res 72:1481–1484

    PubMed  CAS  Google Scholar 

  • Reuterving CO (1986) Pilocarpine-stimulated salivary flow rate and salivary glucose concentration in alloxan diabetic rats. Influence of severity and duration of diabetes. Acta Physiol Scand 126(4):511–515

    Article  PubMed  CAS  Google Scholar 

  • Robinson CP, Yamachika S, Alford CE, Cooper C, Pichardo EL, Shah N, Peck AB, Humphreys-Beher MG (1997) Elevated levels of cysteine protease activity in saliva and salivary glands of the nonobese diabetic (NOD) mouse model for Sjögren syndrome. Proc Natl Acad Sci USA 94(11):5767–5771

    Article  PubMed  CAS  Google Scholar 

  • Seraphim PM, Nunes MT, Giannocco G, Machado UF (2007) Age related obesity-induced shortening of GLUT4 mRNA poly(A) tail length in rat gastrocnemius skeletal muscle. Mol Cell Endocrinol 276:80–87

    Article  PubMed  CAS  Google Scholar 

  • Sharon A, Ben-Aryeh H, Itzhak B, Yoram K, Szargel R, Gutman D (1985) Salivary composition in diabetic patients. J Oral Med 40(1):23–26

    PubMed  CAS  Google Scholar 

  • Takai N, Yoshida Y, Kakudo Y (1983) Secretion and re-absorption of glucose in rat submandibular and sublingual saliva. J Dent Res 62(10):1022–1025

    PubMed  CAS  Google Scholar 

  • Tarpey PS, Wood IS, Shirazi-Beechey P, Beechey RB (1995) Amino acid sequence and the cellular location of the Na+-dependent D-glucose symporters (SGLT1) in the ovine enterocyte and the parotid acinar cell. Biochem J 312:293–300

    PubMed  CAS  Google Scholar 

  • Thorens B (1996) Glucose transporters in the regulation of intestinal, renal and liver glucose fluxes. Am J Physiol 270:541–553

    Google Scholar 

  • Vernillo AT (2001) Diabetes mellitus: relevance to dental treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91:263–270

    Article  PubMed  CAS  Google Scholar 

  • Vestri S, Okamoto MM, Freitas HS, Aparecida dos Santos R, Nunes MT, Morimatsu M, Heimann JC, Machado UF (2001) Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat. J Membr Biol 182:105–112

    Article  PubMed  CAS  Google Scholar 

  • Wright EM (2001) Renal Na(+)-glucose cotransporters. Am J Physiol 280:10–18

    Google Scholar 

  • Wright EM, Loo DF, Hirayama BA, Turk E (2004) Surprising versatility of Na+-glucose cotransporters: SLC5. Physiology 19:370–376

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Adauri Brezolin for careful English revision of the manuscript. This research was supported by FAPESP Grant 07/50554-1. R. Sabino-Silva was the recipient of FAPESP fellowship 06/60833-2.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to U. F. Machado.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabino-Silva, R., Freitas, H.S., Lamers, M.L. et al. Na+-Glucose Cotransporter SGLT1 Protein in Salivary Glands: Potential Involvement in the Diabetes-Induced Decrease in Salivary Flow. J Membrane Biol 228, 63–69 (2009). https://doi.org/10.1007/s00232-009-9159-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-009-9159-3

Keywords

Navigation