title: Expression of Na+-D-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences.
abstract: With a novel antibody against the rat Na(+)-D-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ∼75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and prevented by testosterone treatment. In the renal BBM vesicles, the rSGLT1-independent uptake of [(14)C]-α-methyl-D-glucopyranoside was similar in females and males, suggesting functional contribution of another Na(+)-D-glucose cotransporter to glucose reabsorption. Since immunoreactivity of rSGLT2-Ab could not be detected with certainty in rat extrarenal organs, the SGLT2 protein was immunocharacterized with the same antibody in wild-type (WT) mice, with SGLT2-deficient (Sglt2 knockout) mice as negative control. In WT mice, renal localization of mSGLT2 protein was similar to that in rats, whereas in extrarenal organs neither mSGLT2 protein nor mSglt2 mRNA expression was detected. At variance to the findings in rats, the abundance of mSGLT2 protein in the mouse kidneys was male dominant, whereas the expression of mSglt2 mRNA was female dominant. Our results indicate that in rodents the expression of SGLT2 is kidney-specific and point to distinct sex and species differences in SGLT2 protein expression that cannot be explained by differences in mRNA.
authors.affiliation: Molecular Toxicology, Institute for Medical Research and Occupational Health, Zagreb, Croatia. sabolic@imi.hr
authors.forename: Ivan
authors.initials: I
authors.lastname: Sabolic
authors.forename: Ivana
authors.initials: I
authors.lastname: Vrhovac
authors.forename: Daniela Balen
authors.initials: DB
authors.lastname: Eror
authors.forename: Maria
authors.initials: M
authors.lastname: Gerasimova
authors.forename: Michael
authors.initials: M
authors.lastname: Rose
authors.forename: Davorka
authors.initials: D
authors.lastname: Breljak
authors.forename: Marija
authors.initials: M
authors.lastname: Ljubojevic
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Brzica
authors.forename: Anne
authors.initials: A
authors.lastname: Sebastiani
authors.forename: Serge C
authors.initials: SC
authors.lastname: Thal
authors.forename: Christoph
authors.initials: C
authors.lastname: Sauvant
authors.forename: Helmut
authors.initials: H
authors.lastname: Kipp
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Hermann
authors.initials: H
authors.lastname: Koepsell
mesh_terms: D000818:Animals; D002369:Castration / Q000379:methods; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D051297:Sodium-Glucose Transporter 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D051297:Sodium-Glucose Transporter 2; D027981:Symporters; D013739:Testosterone; D004958:Estradiol; D005947:Glucose; D005690:Galactose