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Renal expression and localization of sodium-d-glucose cotransporter 1 (SGLT1) is different in rats and mice

SGLT1 is a high affinity/low capacity transporter of glucose (G) in the mammalian small intestine and kidneys. In the small intestine, SGLT1 is responsible for the entire G absorption, whereas in kidneys, it contributes to ~10% of G reabsorption, the bulk being handled by the low affinity/high capacity SGLT2. In our recent studies in rat kidneys (Am J Physiol Renal Physiol 290:F913, 2006 & Am J Physiol Cell Physiol 295:C475, 2008), the SGLT1 protein was characterized with the rat-specific polyclonal antibody, and immunolocalized to the proximal tubule (PT) brush border membrane (BBM) and intracellular organelles, exhibiting segmental (S1<S2<S3), zonal (cortex<outer stripe), and sex (females (F)>males (M)) differences in expression. Specific immunoreactivity was also observed in the luminal membrane of cortical thick ascending limb of Henle (TALH) and macula densa. However, previous studies in mice did not reveal clear expression and localization of SGLT1 in their kidneys and other organs due to lack of specific antibody. In order to characterize the SGLT1 protein in mouse organs, we have generated a novel polyclonal antibody against the mouse SGLT1 (mSGLT1-ab). Specificity of the antibody was confirmed by Western blotting (WB) of BBM isolated from the mouse small intestine and kidneys, and by immunostaining of tissue cryosections using wild type (WT) and Sglt1 knockout (KO) mice. In WT mice, mSGLT1-ab labeled the ~75 kDa protein band in the BBM from the small intestine and kidneys, and stained the brush-border of epithelial cells in both organs, whereas in KO mice, both the protein band and immunostaining were absent. In the kidneys of WT mice, the antibody strongly stained the BBM of PT S2 and S3 segments (S1 was negative), exhibiting segmental (S2>S3) and zonal (cortex>outer stripe) differences in staining intensity, similar in both sexes. The SGLT1-ab further stained the apical domain of TALH in the kidney cortex and outer stripe, liver bile ducts, and pancreatic ducts. In these organs, as well as in the small intestine, similar staining intensity in F and M was observed. The cells of macula densa remained unstained. Other tested extrarenal organs, such as brain, spleen, skeletal and heart muscles, and eyes were negative. Therefore, comparison of the data in rats and mice indicates the presence of species differences in renal expression and localization of SGLT1 protein.

sodium-D-glucose cotransporter 1; mammalian kidney; sex differences; species differences

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