SLC5A1

SLC5A1 is the gene that encodes the sodium/glucose cotransporter 1 (SGLT1), a member of the solute carrier 5 (SLC5) family. SGLT1 functions as a sodium-dependent transporter that mediates the uptake of glucose and galactose from the intestinal lumen and, to a lesser extent, the reabsorption of glucose from the renal filtrate.

In humans, SGLT1 is primarily expressed on the apical (luminal) membrane of enterocytes in the small intestine, particularly the duodenum and jejunum, where it plays a key role in dietary carbohydrate absorption. It is also present in the proximal tubule cells of the kidney, contributing to renal glucose reabsorption. SGLT1 uses the inward sodium gradient, maintained by Na+/K+-ATPase, to drive active transport of glucose and galactose against their concentration gradients. It has high affinity for glucose but lower overall transport capacity than other sodium-glucose cotransporters.

Genetic mutations in SLC5A1 cause glucose-galactose malabsorption (GGM), a rare inherited disorder characterized by severe osmotic diarrhea and dehydration in infancy after ingestion of glucose or galactose-containing foods. Management centers on dietary restriction of glucose and galactose to prevent symptoms, often requiring lifelong dietary modification.

Beyond inherited disease, SGLT1 function informs therapeutic strategies; inhibitors of SGLT1 are researched and, in some contexts, combined with SGLT2 inhibitors to reduce intestinal glucose absorption for diabetes management. Inhibition must balance glycemic control with potential gastrointestinal side effects due to unabsorbed sugars.