Sodium Glucose Cotransporter 2 Inhibition in the Diabetic Kidney

An Update

Aleksandra Novikov; Volker Vallon


Curr Opin Nephrol Hypertens. 2016;25(1):50-58. 

In This Article

Sodium Glucose Cotransporter 2 and Renal Glucose Reabsorption in Normoglycemia

Under conditions of normal serum glucose levels and glomerular filtration rate (GFR), about 160–180 g of glucose is filtered each day and nearly completely reabsorbed by the kidneys. The sodium glucose transporters SGLT2 and SGLT1 in the luminal membrane of the proximal tubule have been established as the primary mechanisms of glucose reabsorption in the kidney[4–6] (Fig. 2). Using validated antibodies and knockout mice as negative controls, the SGLT2 protein has been localized in the luminal membrane of the early proximal tubule (S1 and S2 segments), whereas the SGLT1 protein is expressed in the late proximal tubule (S3 segment) in rodents.[7,8] Recent studies using well validated antibodies confirmed this expression pattern in the human kidney, and found that, in contrast to rodents, renal SGLT2 expression was sex-independent.[9]

Studies in knockout mice demonstrated that SGLT2 is responsible for all glucose reabsorption in the early proximal tubule and for most kidney glucose reabsorption overall,[7] whereas SGLT1 reabsorbs 3% of the filtered glucose in euglycemia.[10] Net renal glucose reabsorption is absent during pharmacologic SGLT2 inhibition in SGLT1-/- mice, as well as in SGLT1/SGLT2 double knockout mice,[11] indicating that SGLT2 and SGLT1 can explain all renal glucose reabsorption in euglycemia and that SGLT2 reabsorbs ~97% in euglycemia.