engleski

Sex-and species-dependent expression of renal sodium-glucose cotransporter 2 (SGLT2)in rats and mice

Reabsorption of glucose in the renal proximal tubule is of pivotal physiological importance in health and disease. The reabsorption of glucose from ultrafiltrate prevents loss of metabolic energy and is important for glucose homeostasis and sodium and water balance [1]. For almost 2 decades, there is a huge interest in therapies to treat diabetic patients, and one is to control blood glucose by inhibiting Sglt2 in the kidney [2]. Sglt2 (slc5a2) is responsible for the majority of glucose reabsorption in the mammalian renal proximal tubule (PT). In our previous studies [3] in rat kidneys we confirmed the Sglt2 protein (rSglt2) expression in the brush border membrane (BBM) of cortical PT S1 and S2 segments with the female (F)-dominant sex differences (Figure 1.). In order to test the presence and determine localization of Sglt2 protein in mouse kidneys (mSglt2), two different polyclonal antibodies, rSglt2-Ab (cross-reacts with mSglt2-Ab) and mSglt2-Ab, were used in immunochemical studies. Usefulness and specificity of the antibodies for mSglt2 was proven by a) Western blotting (WB) of isolated whole kidney total cell membranes (TCM) and brush-border membranes (BBM) ; the antibodies labeled a single protein band of ~75 kDa in the membranes from adult wild-type (WT) mouse kidneys, b) immunofluorescence cytochemistry (IC) in tissue cryosections of the formalin-fixed kidneys ; the antibodies stained the brush-border of cortical PT S1 and S2 segments in WT animals, and c) absence of the labeled protein band and IC staining when using the immunizing peptide-blocked antibodies or membrane and tissue samples from the mSglt2 knockout (KO) mice (Figure 2.). In adult WT mice, the IC studies revealed the male (M)-dominant staining intensity of the renal Sglt2. Accordingly, in WB of the renal TCM and BBM, the density of mSglt2 protein band was significantly stronger in M then in F, whereas the band density of α-actin was similar in membranes from both sexes (Figure 3.).We conclude that in mice the renal Sglt2 protein expression exhibits sex differences (M > F) which are opposite from those in rats (M < F). The presence of sex- and species-related differences in renal transporters, such as shown here for Sglt2 in rats and mice, leaves doubts whether these animals are good experimental models for physiological and pharmacological studies in humans.

kidney, knock-out mice, membrane transporters, western blotting, sex differences

nije evidentirano