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Pflügers Archiv - European Journal of Physiology

, Volume 467, Issue 9, pp 1881–1898 | Cite as

Localizations of Na+-d-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart

  • Ivana Vrhovac
  • Daniela Balen Eror
  • Dirk Klessen
  • Christa Burger
  • Davorka Breljak
  • Ognjen Kraus
  • Nikola Radović
  • Stipe Jadrijević
  • Ivan Aleksic
  • Thorsten Walles
  • Christoph Sauvant
  • Ivan Sabolić
  • Hermann Koepsell
Ion channels, receptors and transporters

Abstract

Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.

Keywords

Clara cells Enteroendocrine cells Human organs Immunolocalization mRNA expression Na+-d-glucose cotransport Proximal tubules Sex differences 

Notes

Acknowledgments

The authors acknowledge the technical help by Mrs. Eva Heršak. This work was supported by the grant 022-0222148-2146 from Croatian Ministry for Science, Education and Sports (I.S.) and by Deutsche Forschungsgemeinschaft Grant KO 872/5-1 (H.K.).

Supplementary material

424_2014_1619_MOESM1_ESM.doc (5.7 mb)
ESM 1 (DOC 5,864 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ivana Vrhovac
    • 1
  • Daniela Balen Eror
    • 1
  • Dirk Klessen
    • 2
  • Christa Burger
    • 3
  • Davorka Breljak
    • 1
  • Ognjen Kraus
    • 4
  • Nikola Radović
    • 5
  • Stipe Jadrijević
    • 6
  • Ivan Aleksic
    • 7
  • Thorsten Walles
    • 7
  • Christoph Sauvant
    • 8
  • Ivan Sabolić
    • 1
  • Hermann Koepsell
    • 9
  1. 1.Molecular Toxicology UnitInstitute for Medical Research and Occupational HealthZagrebCroatia
  2. 2.Institute of Anatomy and Cell BiologyUniversity of WürzburgWürzburgGermany
  3. 3.Merck KgaADarmstadtGermany
  4. 4.Clinical Hospital Sisters of MercyZagrebCroatia
  5. 5.Clinical Hospital DubravaZagrebCroatia
  6. 6.Clinical Hospital MerkurZagrebCroatia
  7. 7.Department of Thoracic and Cardiovascular SurgeryUniversity Hospital of WürzburgWürzburgGermany
  8. 8.Department of Anesthesiology and Critical Care MedicineUniversity Hospital HalleHalleGermany
  9. 9.Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute, Institute of Anatomy and Cell BiologyUniversity of WürzburgWürzburgGermany

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