TY - JOUR
T1 - Kidney in diabetes
T2 - From organ damage target to therapeutic target
AU - Salvatore, Teresa
AU - Carbonara, Ornella
AU - Cozzolino, Domenico
AU - Torella, Roberto
AU - Nasti, Rodolfo
AU - Lascar, Nadia
AU - Sasso, Ferdinando Carlo
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Antidiabetic drugs
KW - Dapagliflozin
KW - Kidney
KW - SGLT2 inhibitors
KW - Sodium-glucose cotransporters
KW - Type 2 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=79961083208&partnerID=8YFLogxK
UR - https://www.eurekaselect.com/74677/article
U2 - 10.2174/138920011796504509
DO - 10.2174/138920011796504509
M3 - Review article
C2 - 21495978
AN - SCOPUS:79961083208
SN - 1389-2002
VL - 12
SP - 658
EP - 666
JO - Current Drug Metabolism
JF - Current Drug Metabolism
IS - 7
ER -