Familial Renal Glucosuria and SGLT2: From a Mendelian Trait ... : Clinical Journal of the American Society of Nephrology (original) (raw)
In-Depth Reviews: In-Depth Reviews
Familial Renal Glucosuria and SGLT2
From a Mendelian Trait to a Therapeutic Target
*Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
†Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal; and
‡Department of Nephrology, Hospital de Curry Cabral, Lisbon, Portugal
Correspondence: Dr. Joaquim Calado, Department of Genetics, Faculty of Medical Sciences, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua da Junqueira no 96, 1349-008, Lisbon, Portugal. Phone: 351-213610297; Fax: 351-213622018; E-mail: [email protected]
Abstract
Four 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 m2 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.
Copyright © 2010 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
Full Text Access for Subscribers:
