SGLT1

SGLT1 (SLC5A1) is a sodium-glucose cotransporter that mediates intestinal D-glucose and D-galactose uptake across the brush-border membrane^[1]. Mechanistically, SGLT transport uses the sodium electrochemical gradient to drive uphill glucose movement across the plasma membrane^[2]. In mouse models, SGLT1 supports intestinal glucose absorption, glucose-dependent GIP and GLP-1 secretion, and about 3% of filtered renal glucose reabsorption under normoglycemia^[3]. In disease relevance, defects in intestinal Na⁺-dependent glucose absorption cause glucose-galactose malabsorption with severe diarrhea and dehydration^[4]. Compared with SGLT2, SGLT1 is mainly linked to intestinal absorption and later proximal-tubule glucose recovery, whereas SGLT2 mediates bulk renal glucose reabsorption in early proximal tubule segments^[5]. For experimental applications, SGLT1 inhibition lowers and delays post-carbohydrate glucose excursion and can augment GLP-1 and PYY secretion, making SGLT1 inhibitors useful probes for intestinal glucose transport and enteroendocrine responses^[1]. Structural studies of human SGLT1 with LX2761 provide a framework for studying inhibitor binding and transporter pharmacology^[2].