engleski

Inhibitors of glucose transporter SGLT1 in the treatment of diabetes mellitus will not act only in the kidneys ; the transporter is also present in other rodent and human organs

Diabetes mellitus, one of the most common chronic diseases in population, is becoming a major health and economic problem. Current therapies with insulin and metformin, aimed at reducing blood glucose, are often ineffective and/or problematic due to the induction of hypoglycemia, body weight gain, and occasional death resulting from cardiovascular disease. A novel generation of oral anti-diabetics inhibits sodium-D-glucose cotransporters in the small intestine (SGLT1/SLC5A1), thus diminishing the absorption of glucose from the diet, as well as in the kidneys(SGLT1 and/or SGLT2/SLC5A2), thus decreasing glucose reabsorption along the nephron and enhancing its excretion through urine. Overall, this improves glycemia, reduces body weight, lowers blood pressure, and decreases damage to the cardiovascular system. However, our recent studies showed that in humans, SGLT1 is not expressed only in the intestinal and renal epithelium ; it was also detected in the liver (bile duct epithelium), lungs (bronchiolar Clara cells and alveolar type II cells), and heart (blood capillaries). These places represent possible targets for novel SGLT1 inhibitors. SGLT1 or dual (SGLT1+SGLT2) inhibitors may inhibit various SGLTs-related functions, such as fluid absorption in the lungs, energy supply to Clara cells, and glucose release from the heart capillaries, and may thus cause functional disorders. In addition, our novel unpublished data showed that in mice, Sglt1 is localized in the kidneys, small intestine, liver, pancreas, salivary glands, tongue, prostate, seminal vesicles, and uterus. The newly discovered localizations of SGLT1/Sglt1 suggest certain novel functions for this transporter, which could be of great physiological and biomedical importance.

human organs; immunocytochemistry; mouse organs; qRT-PCR; sodium-D-glucose cotransporters; SGLT1; SGLT2

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