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No extrarenal expression of SGLT2 and sex differences in renal expression
Author(s) -
Rose Michael,
Gerasimova Maria,
Cunard Robyn,
Koepsell Hermann,
Sabolic Ivan,
Vallon Volker
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1099.5
Subject(s) - medicine , endocrinology , messenger rna , kidney , spleen , pancreas , real time polymerase chain reaction , gene expression , biology , gene , biochemistry
Inhibitors of the sodium glucose cotransporter SGLT2 in the proximal tubule have been developed as new anti‐diabetic drugs. Whether SGLT2 also has extrarenal expression is unclear. Here we analyzed SGLT2 protein and mRNA expression in male and female mice (lung, spleen, brain, cerebellum, eye, intraperitoneal fat, heart, testis, uterus, jejunum, submaxillary gland, liver, skeletal muscle and pancreas), and used wild‐type (WT) kidneys and organs of Sglt2 knockout (−/−) mice as positive and negative controls, respectively. A TaqMan® gene expression assay was performed in a real time PCR system and amplification efficiencies standardized against rpl19. Sglt2 mRNA was consistently expressed in WT kidney (Ct value 23.1±0.1) but not detected in other organs at up to 50 cycles. The SGLT2 antibody recognized a specific band close to the predicted size in kidneys of WT but not Sglt2 −/− mice. In none of the extrarenal WT organs did the antibody detect a band that corresponded in size to SGLT2 and was unique to WT vs Sglt2 −/− mice. Additional studies revealed a 27% lower renal SGLT2 protein expression in females vs males (n=6/gender; P=0.007 ) despite a 49% higher Sglt2 mRNA expression in female kidneys ( P=0.006 ). The results argue against the expression of SGLT2 mRNA or protein in the extrarenal organs and point to a significant sex difference in renal SGLT2 protein expression that is not explained by different mRNA levels.