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

PLoS One. 2016 Mar 21;11(3):e0151585. doi: 10.1371/journal.pone.0151585. eCollection 2016.

Abstract

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.

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Blotting, Western
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Extracellular Space / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Mesangial Cells / cytology
  • Mesangial Cells / metabolism*
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Sodium / metabolism
  • Sodium-Glucose Transporter 2 / metabolism*
  • Time Factors

Substances

  • Calcium Channel Blockers
  • Slc5a2 protein, rat
  • Sodium-Glucose Transporter 2
  • Angiotensin II
  • Sodium
  • Glucose
  • Calcium

Grants and funding

The authors have no support or funding to report.