Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart - PubMed (original) (raw)
. 2015 Sep;467(9):1881-98.
doi: 10.1007/s00424-014-1619-7. Epub 2014 Oct 11.
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
Affiliations
- PMID: 25304002
- DOI: 10.1007/s00424-014-1619-7
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 et al. Pflugers Arch. 2015 Sep.
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.
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References
- Cell Tissue Res. 1992 Jan;267(1):3-9 - PubMed
- Cardiovasc Res. 2009 Oct 1;84(1):111-8 - PubMed
- Physiol Rev. 2011 Apr;91(2):733-94 - PubMed
- J Clin Invest. 1974 Feb;53(2):526-35 - PubMed
- J Neurochem. 1997 Jul;69(1):84-94 - PubMed
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