The Na(+)/glucose cotransporters: from genes to therapy.

Glucose enters eukaryotic cells via two types of membrane-associated carrier proteins, the Na(+)/glucose cotransporters (SGLT) and the facilitative glucose transporters (GLUT). The SGLT family consists of six members. Among them, the SGLT1 and SGLT2 proteins, encoded by the solute carrier genes SLC5A1 and SLC5A2, respectively, are believed to be the most important ones and have been extensively explored in studies focusing on glucose fluxes under both physiological and pathological conditions. This review considers the regulation of the expression of the SGLT promoted by protein kinases and transcription factors, as well as the alterations determined by diets of different compositions and by pathologies such as diabetes. It also considers congenital defects of sugar metabolism caused by aberrant expression of the SGLT1 in glucose-galactose malabsorption and the SGLT2 in familial renal glycosuria. Finally, it covers some pharmacological compounds that are being currently studied focusing on the interest of controlling glycemia by antagonizing SGLT in renal and intestinal tissues.

Effect of phlorizin on SGLT2 expression in the kidney of diabetic rats.

BACKGROUND: The purpose of our study was to determine whether increased SGLT2 expression in the kidney of diabetic rats was associated with the development of hypertension and to investigate the effect of phlorizin (P) on blood pressure and SGLT2 expression in diabetic rats. METHODS: The animals were divided into two groups: Control (C) and streptozotocin-induced diabetic (D) rats were used to evaluate SGLT2 activity in brush border membrane vesicles (BBMV) using a rapid filtration technique. Others animals were divided into two groups: Normal (NSD) or high salt diet (4%)(HSD), and subdivided in four groups: C, C+P, D, D+P. Systolic blood pressure (SBP) was recorded for 30 days by the use of a telemetric system and at day 30 urine samples (24 h) were collected to evaluate renal function and SGLT2 expression in the renal cortex. RESULTS: At day 30, diabetic animals with NSD or HSD exhibited hyperglycemia, lower body weight, glycosuria, diuresis, decrease natriuresis, increased SBP values and SGLT2 expression. In diabetic rats, phlorizin treatment decreased hyperglycemia and prevented development of hypertension, decreased SGLT2 activity in BBMV but did not modify SGLT2 expression. CONCLUSIONS: In conclusion, SGLT2 inhibition prevented the development of hypertension in diabetic rats as well as hyperglycemia, suggesting a hypertensive mechanism associated with SGLT2 activity and the likelihood that increased SGLT2 expression may be associated with progression of diabetic renal complications.