SODIUM-GLUCOSE TRANSPORTER 2 INHIBITION – A POTENTIAL OPTION FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS
Journal Title: Romanian Journal of Diabetes Nutrition and Metabolic Diseases - Year 2011, Vol 18, Issue 1
Abstract
Glucose homeostasis is maintained by the balanced actions of glucose absorption, gluconeogenesis, glycogenolysis, glucose consumption, glucose excretion and glucose reabsorption. The human kidney is involved in glucose regulation by three mechanisms: gluconeogenesis, uptake of glucose and reabsorption of glucose at the level of the proximal tubule. Transporters of two gene families are responsible for the absorption of glucose from the glomerular filtrate: glucose transporters (GLUT) and sodium-glucose transporters (SGLT). Approximately 90% of the glucose is reabsorbed in the first segment of the proximal tubule, where GLUT2 and SGLT2 are expressed, and approximately 10% is reabsorbed in the third segment of the proximal tubule, where GLUT1 and SGLT1 are expressed. In patients with diabetes, the kidney reabsorbs as much glucose as possible from the filtered fluid. An in vitro study of cultured human renal proximal tubular cells isolated from urine of patients with type 2 diabetes showed an increased expression of GLUT2 and SGLT2 and a higher threshold for glucose reabsorbtion by comparison with non-diabetics. Development of inhibitors with a high specificity for SGLT2 represents a potential option in the treatment of diabetes. In patients with type 2 diabetes, SGLT-2 inhibition is associated with dose-related decrements in glycosylated hemoglobin level and modest weight loss. SGLT-2 inhibition decreases systolic and diastolic blood pressure and serum uric acid concentration. The treatment with SGLT-2 inhibitors increases urinary volume and hematocrit. Prolonged glycosuria is a risk factor for development of genito-urinary infections and an approximate doubling of episodes of vulvo-vaginitis and balanitis has been reported. Monitoring of adverse effects is important for the patient safety in this class of drugs. Potential extrarenal effects need to be explored and potential progression of renal dysfunction will have to be monitored.
Authors and Affiliations
Rucsandra Dănciulescu Miulescu, Liviu Șerb
Keywords
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