SGLT as a therapeutic target

The expression of the sodium/glucose cotransporter (SGLT), a membrane protein, is limited to renal tubules and the intestinal basolateral membrane. A classic competitive inhibitor of SGLT, phlorizin, given by injection reportedly exerts a hypoglycemic effect in diabetic rodents via induction of glycosuria. Unlike phlorizin, the recently developed phlorizin derivative T-1095 is effectively absorbed in the gut and enters the circulation after oral administration. Similar to injected phlorizin, orally administered T-1095 lowers blood glucose in diabetic animals by enhancing urinary glucose excretion via suppression of renal SGLT function. In addition to this acute hypoglycemic action, chronic T-1095 treatment induces other effects favoring the restoration of impaired insulin secretion from pancreatic beta-cells and normalization of hyperglycemia-induced insulin resistance in muscle and liver. In addition, it is possible that correcting hyperglycemia with this SGLT inhibitor may contribute to the prevention and treatment of diabetic complications. Thus, oral SGLT inhibitors are a promising new class of antidiabetic drugs.