SGLT2SLC5A2

SGLT2, or SLC5A2, refers to the renal sodium-glucose cotransporter 2, a member of the solute carrier 5 (SLC5) family. The protein is a multi-pass transmembrane transporter expressed predominantly in the apical membrane of proximal tubule cells in the kidney, especially in the S1/S2 segments, where it facilitates the uptake of glucose from the filtrate in a sodium-dependent manner.

Functionally, SGLT2 reabsorbs the majority of filtered glucose from urine back into the bloodstream, coupling glucose transport to the sodium gradient established by the basolateral Na+/K+ ATPase. This activity helps maintain glucose homeostasis and minimizes urinary glucose loss under normal conditions. Pharmacological inhibition of SGLT2 reduces glucose reabsorption, leading to glucosuria and a modest diuretic effect independent of insulin.

Clinically, SGLT2 inhibitors (the gliflozins) target SGLT2 to improve glycemic control in type 2 diabetes mellitus and have demonstrated benefits in heart failure and chronic kidney disease, even in patients without diabetes. Examples include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Potential adverse effects include increased risk of genital and urinary tract infections, dehydration from osmotic diuresis, and, in rare cases, euglycemic ketoacidosis.

Genetically, mutations in SLC5A2 can cause familial renal glycosuria, a condition in which glucose is excreted in the urine despite normal or near-normal blood glucose levels. The SLC5A2/SGLT2 axis remains an area of active research, with interest in broader metabolic and renal protective roles.