Sodium Glucose Cotransporter 2 (SGLT2) Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells

PURPOSE Mesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT) in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2. METHODS The SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX) inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor. RESULTS Western blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction. CONCLUSIONS These data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells.