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 Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic  target Santer R; Calado JClin J Am Soc Nephrol  2010[Jan]; 5 (1): 133-41Four members of two glucose transporter families, SGLT1, SGLT2, GLUT1, and GLUT2,  are differentially expressed in the kidney, and three of them have been shown to  be necessary for normal glucose resorption from the glomerular filtrate.  Mutations in SGLT1 are associated with glucose-galactose malabsorption, SGLT2  with familial renal glucosuria (FRG), and GLUT2 with Fanconi-Bickel syndrome.  Patients with FRG have decreased renal tubular resorption of glucose from the  urine in the absence of hyperglycemia and any other signs of tubular dysfunction.  Glucosuria in these patients can range from <1 to >150 g/1.73 m(2) per d. The  majority of patients do not seem to develop significant clinical problems over  time, and further description of specific disease sequelae in these individuals  is reviewed. SGLT2, a critical transporter in tubular glucose resorption, is  located in the S1 segment of the proximal tubule, and, as such, recent attention  has been given to SGLT2 inhibitors and their utility in patients with type 2  diabetes, who might benefit from the glucose-lowering effect of such compounds. A  natural analogy is made of SGLT2 inhibition to observations with inactivating  mutations of SGLT2 in patients with FRG, the hereditary condition that results in  benign glucosuria. This review provides an overview of renal glucose transport  physiology, FRG and its clinical course, and the potential of SGLT2 inhibition as  a therapeutic target in type 2 diabetes.|Diabetes Mellitus, Type 2/drug therapy/genetics[MESH]|Glycosuria/*drug therapy/*genetics[MESH]|Humans[MESH]|Kidney/metabolism[MESH]|Sodium-Glucose Transporter 2 Inhibitors[MESH]|Sodium-Glucose Transporter 2/*genetics/physiology[MESH]
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