Sodium-glucose cotransporter protein type 1 (SGLT1)

Sodium-glucose cotransporter protein type 1 (SGLT1) is an integral membrane protein encoded by the SLC5A1 gene that mediates the active, sodium-dependent uptake of glucose and galactose across the brush-border membrane of intestinal epithelial cells and the late segments of the renal proximal tubule[1][2][3][4][5][6][7]. Utilizing a secondary active transport mechanism, SGLT1 couples the inward movement of two sodium ions with one glucose molecule—enabling energy-dependent accumulation of glucose against its concentration gradient[5][7]. This activity is critical for nutrient absorption from the diet, renal glucose salvage, and the maintenance of systemic glucose homeostasis[2][4][6]. SGLT1 is a validated therapeutic target for diabetes and obesity: specific inhibitors block glucose absorption in the gut and decrease renal glucose reabsorption[5]. Mutations in SGLT1 lead to glucose-galactose malabsorption, a rare but severe inherited disorder[2]. SGLT1’s structure features 14 transmembrane α-helices, forming a channel through which glucose and sodium are cotransported; it participates in protein-protein interactions and its function is regulated by phosphorylation and membrane lipid composition[1][3][4].

Other names

Solute carrier family 5 member 1SLC5A1Sodium/glucose cotransporter 1Na+/glucose cotransporter 1NAGTSC5A1_HUMAN

Inhibition reduces intestinal absorption of glucose and galactose. Inhibition decreases renal glucose reuptake, increasing urinary glucose excretion. Inhibitors act by blocking sodium-coupled cotransport at the substrate-binding site. Lower blood glucose by preventing glucose entry into blood from gut and kidney.