engleski

Sodium-glucose cotransporter Sglt1 (Slc5a1) is present in various murine organs : sex-related expression in kidneys

Diabetes mellitus affects ~400 million people worldwide. Novel antidiabetic drugs have been developed aiming to lower blood glucose by inhibiting the activity of sodium-D-glucose cotransporter 1 (SGLT1 in humans/Sglt1 in rodents) in the intestine and kidney. In rodents, the intestinal Sglt1, localized in the enterocyte brush-border membrane (BBM), is responsible for bulk (>80%) glucose absorption, whereas the renal transporter, localized in the proximal tubule (PT) cell BBM, contributes to minor (~3%) glucose reabsorption. The presence of Sglt1 in other organs is poorly known. As mice are frequently used experimental animals in preclinical studies, knowledge of the Sglt1 distribution in various organs as possible targets of new inhibitors may be of great importance. Here we compared the expression of Sglt1 mRNA and protein in various organs of wild type (WT/Sglt1+/+) and Sglt1 knockout (KO/Sglt1-/-) mice by qRT-PCR and immunocytochemistry (IC). In WT mice, the Sglt1 mRNA expression was highest in small intestine ; high in seminal vesicle, kidney and salivary glands ; medium in prostate, tongue, eyes and uterus, and small in pancreas, lung and liver. By IC, Sglt1 protein was detected in small intestine (enterocyte BBM), kidney (PT BBM and apical membrane (AM) of thick ascending limb of Henle), liver (bile ducts, AM), pancreas (ducts, AM), salivary glands (serous acini and initial ducts, AM), tongue (taste epithelium), prostate (epithelial cells, AM), bulbourethral gland (ducts, AM), seminal vesicles (intracellular organelles in epithelial and basal cells), and uterus (endometrium, AM). In PT, the staining intensity was 3-fold higher in BBM of S2 segments in the cortex compared to S3 segments in the outer stripe. However, the opposite sex-dependent expression was observed for the renal Sglt1 mRNA (females > males) and its protein (males > females) indicating different transcriptional and post-translational regulations. The presence of Sglt1 in various organs indicates that the potential inhibitors of SGLT1 activity in diabetic humans may target these localizations with unpredictable health consequences.

qRT-PCR ; immunocytochemistry ; Sglt1 knockout ; glucose transport ; sex differences

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