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Species differences in the expression of sodium-D-glucose cotransporter 1 (SGLT1/SLC5A1), a potential therapeutic target in diabetes

Cellular uptake and metabolism of glucose (G) serves as an important energy source. In mammals, SGLT1 (humans)/Sglt1 (rodents) mediates an almost complete absorption of G in small intestine (SI) and a limited (3-15%) reabsorption of G in kidneys (K). Novel antidiabetic drugs were recently developed aiming to lower blood G by inhibiting SGLT1 in SI and K. However, if SGLT1 is expressed in insufficiently explored other organs, these drugs could affect their function and induce health disturbances in diabetic patients. To reveal SGLT1/Sglt1 expression in other organs, we performed mRNA and immunochemical studies in various human, mouse and rat organs. In humans, SGLT1 mRNA was detected in SI, K, liver, lung, and heart, but not in brain, whereas the SGLT1 protein was localized in the luminal membrane (LM) of SI enterocytes, K nephron and hepatic duct cells, in lung alveolar type 2 and bronchiolar Clara cells, and in heart capillaries. In mice, Sglt1 mRNA expression was highest in SI, high in seminal vesicles, K and salivary glands, medium in prostate, tongue, eyes and uterus, and very low in pancreas, lungs, liver, and brain. The Sglt1 protein in wild-type, but not in Sglt1 knockout mice, was immunolocalized in the LM of SI enterocytes, K proximal tubule, liver bile ducts, pancreatic ducts, salivary glands (acinal and duct cells), prostate epithelium, bulbourethral gland ducts, uterine endometrium, tongue taste cells and eyes (optical nerve), while brain, lungs and seminal vesicles were Sglt1-negative. In rats, we localized the Sglt1 protein in SI, K, and submandibular glands (similar to the findings in mice), but also in lungs, brain, and heart capillaries (different from the findings in mice). The novel extrarenal localizations implicate so far unrecognized (patho)physiological roles of SGLT1/Sglt1 in the mammalian organs, indicate species differences in this protein expression in some of them, and represent potential targets for the novel inhibitors. Since the Sglt1 expression in rodents does not fully reflect that in humans, it is thus important to carefully select an animal model for each organ of interest to study the role of SGLT1 in human health and disease.

mouse; rat; human; qPCR; western; immunohistochemistry

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