Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications.
The kidneys play a major role in the regulation of glucose in humans, reabsorbing 99% of the plasma glucose that filters through the renal glomeruli tubules. The glucose transporter, SGLT2, which is found primarily in the S1 segment of the proximal renal tubule, is essential to this process, accounting for 90% of the glucose reabsorption in the kidney. Evidence has suggested that selective inhibition of SGLT2 induces glucosuria in a dose-dependent manner and may have beneficial effects on glucose regulation in individuals with type II diabetes. Preclinical data with SGLT2 inhibitors, such as dapagliflozin and sergliflozin, show that these compounds are highly selective inhibitors for SGLT2, have beneficial effects on the glucose utilization rate, and reduce hyperglycemia while having no hypoglycemic adverse effects. Clinical research remains to be carried out on the long-term effects of glucosuria and other potential effects of this class of drug. Nonetheless, these compounds represent a very promising approach for the treatment of diabetes.
Bakris
George L
GL
Hypertensive Diseases Unit, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA. Electronic address: gbakris@gmail.com.
Fonseca
Vivian A
VA
Department of Medicine and Pharmacology, Tulane University Health Sciences Center, New Orleans, Los Angeles, USA.
Sharma
Kumar
K
Department of Medicine, University of California at San Diego/VA Medical System, La Jolla, California, USA.
Wright
Ernest M
EM
Department of Physiology, Mellinkoff Professor in Medicine, Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D051247:Sodium-Glucose Transport Proteins / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics / Q000378:metabolism*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D012333:RNA, Messenger; C089180:SLC5A2 protein, human; D051247:Sodium-Glucose Transport Proteins; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D012964:Sodium; D005947:Glucose