The Na/K-ATPase Signaling and SGLT2 Inhibitor-Mediated Cardiorenal Protection: A Crossed Road?

J Membr Biol. 2021 Dec;254(5-6):513-529. doi: 10.1007/s00232-021-00192-z. Epub 2021 Jul 23.

Abstract

In different large-scale clinic outcome trials, sodium (Na+)/glucose co-transporter 2 (SGLT2) inhibitors showed profound cardiac- and renal-protective effects, making them revolutionary treatments for heart failure and kidney disease. Different theories are proposed according to the emerging protective effects other than the original purpose of glucose-lowering in diabetic patients. As the ATP-dependent primary ion transporter providing the Na+ gradient to drive other Na+-dependent transporters, the possible role of the sodium-potassium adenosine triphosphatase (Na/K-ATPase) as the primary ion transporter and its signaling function is not explored.

Keywords: Na/K-ATPase; ROS; SGLT inhibitor; Signaling.

Publication types

  • Review

MeSH terms

  • Glucose
  • Humans
  • Kidney / metabolism
  • Signal Transduction*
  • Sodium / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
  • Glucose