title: Kidney in diabetes: from organ damage target to therapeutic target.
abstract: Despite the growing of pharmacological options for the treatment of diabetes, epidemiological studies suggest that a substantial proportion of patients does not achieve glycemic goals and so suffers from the risk of chronic complications. This review explores the inhibition of renal glucose reabsorption as a novel approach to treat hyperglycemia. Sodium-glucose cotransporter 2 (SGLT2), a low-affinity high-capacity transporter located in the brush-border membrane of the early segment (S1) of the proximal renal tubule, accounts for about 90% of the reabsorption of glucose from tubular fluid. Competitive inhibitors of SGLT2 that are responsible for renal excretion of glucose provide a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. They act independently of insulin secretion, thereby minimizing the risk of hypoglycemia and weight gain, to control energy balance in a negative direction, a distinctive advantage of this class of drugs over existing oral hypoglycemic agents. Although this group of medications is still under investigation, it appears to be safe and generally well tolerated and it would be expected to improve the treatment of type 2 diabetes as monotherapy or in combination with other oral or parenteral agents. Dapagliflozin is the first agent within this class, which induces clinically meaningful reductions in FPG, PPG, HbA1c, and body weight in type 2 diabetes.
authors.affiliation: Dept. of Internal and Experimental Medicine Second University of Naples, Italy, Via F. Petrarca, 64, I- 80122 Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Salvatore
authors.forename: Ornella
authors.initials: O
authors.lastname: Carbonara
authors.forename: Domenico
authors.initials: D
authors.lastname: Cozzolino
authors.forename: Roberto
authors.initials: R
authors.lastname: Torella
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Nasti
authors.forename: Nadia
authors.initials: N
authors.lastname: Lascar
authors.forename: Ferdinando Carlo
authors.initials: FC
authors.lastname: Sasso
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors