SGLT1

SGLT1, or sodium-glucose cotransporter 1, is a membrane transport protein encoded by the SLC5A1 gene. It is a member of the SLC5 family and typically features multiple transmembrane helices. SGLT1 functions as a sodium-dependent transporter that moves glucose and galactose into cells against their concentration gradients by coupling their uptake to the inward movement of sodium ions.

Localization and mechanism: SGLT1 is predominantly located on the apical (luminal) membrane of enterocytes in the small intestine, where it mediates dietary glucose and galactose absorption. It is also expressed in renal proximal tubules, where it contributes to reabsorption of a portion of filtered glucose. The transporter has a stoichiometry of about 2 Na+ ions per glucose or galactose molecule, using the sodium gradient maintained by Na+/K+-ATPase to drive uptake. It is electrogenic and has high affinity for glucose and galactose, with little transport of fructose.

Physiological role: In the gut, SGLT1 is essential for efficient absorption of dietary carbohydrates and contributes to postprandial glucose levels. In the kidney, it reabsorbs glucose from the filtrate, although the majority of renal glucose reabsorption is carried out by SGLT2 in the proximal tubule; SGLT1 accounts for a smaller but clinically meaningful portion of reabsorption.

Clinical significance: Loss-of-function mutations in SLC5A1 cause glucose-galactose malabsorption (GGM), an autosomal recessive disorder characterized by severe osmotic diarrhoea and dehydration after ingestion of glucose or galactose. Management relies on dietary avoidance of these sugars and, when needed, substitution with fructose.

Pharmacology: SGLT1 inhibitors, including dual SGLT1/2 inhibitors such as sotagliflozin, reduce intestinal glucose absorption and renal glucose reabsorption. They have been studied for diabetes management but can cause gastrointestinal side effects and dehydration; research and clinical use vary by region and indication.