SGLT
Summary
SGLT (Sodium-Glucose Linked Transporter) proteins mediate active transport of glucose across cell membranes coupled with sodium reabsorption. SGLT2 is located in the proximal convoluted tubule (S1 segment) and reabsorbs ~90% of filtered glucose, while SGLT1 in the S3 segment and small intestine reabsorbs the remainder and dietary glucose/galactose. SGLT2 inhibitors are a major class of antidiabetic drugs targeting this transporter.
Detail
SGLT1 and SGLT2 are members of the sodium-glucose cotransporter family that use the sodium gradient (maintained by Na+/K+-ATPase) to drive glucose uptake against its concentration gradient (secondary active transport). SGLT2 is a high-capacity, low-affinity transporter in the early proximal tubule (S1 segment) responsible for the majority of renal glucose reabsorption. SGLT1 is a low-capacity, high-affinity transporter found in the late proximal tubule (S3 segment) and the intestinal brush border, where it absorbs both glucose and galactose. Loss-of-function mutations in SGLT2 cause familial renal glucosuria, while SGLT1 mutations cause glucose-galactose malabsorption (presenting with severe diarrhea in infants relieved by removing glucose/galactose from diet, fructose is tolerated). Clinically, SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) block glucose reabsorption in the kidney, causing glucosuria and lowering blood glucose independent of insulin; they also promote weight loss, reduce blood pressure, and have proven cardiovascular and renal protective effects in diabetic patients (reduced heart failure hospitalizations, slowed progression of diabetic nephropathy). Side effects include genital mycotic infections, urinary tract infections, volume depletion, and rare euglycemic diabetic ketoacidosis. GLUT transporters (facilitated diffusion, not sodium-dependent) are distinct from SGLT transporters and should not be confused (e.g., GLUT1 in RBCs/brain, GLUT2 in liver/pancreas/kidney basolateral, GLUT4 insulin-dependent in muscle/fat).
Sources
- Guyton and Hall Textbook of Medical Physiology
- Katzung's Basic and Clinical Pharmacology
- First Aid for the USMLE Step 1
- UpToDate: SGLT2 inhibitors for diabetes mellitus
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.