Dexamethasone increases Na+/K+ ATPase activity in insulin secreting cells through SGK1

Glucocorticoids blunt insulin release, an effect partially due to activation of Kv channels. Similar to those channels Na+/K+ ATPase activity repolarizes the plasma membrane. The present study explored whether glucocorticoids increase the Na+/K+ ATPase activity in pancreatic β-cells. The glucocorticoid dexamethasone (100 nmol/l for 1 day) significantly increased Na+/K+ ATPase α1/β1-subunit transcript levels and ouabain-sensitive outward current reflecting Na+/K+ ATPase activity in INS-1 cells, effects blunted by glucocorticoid-receptor-blocker RU487 (1 μmol/l). Dexamethasone (100 nmol/l) increased K+ current in β-cells from wild type mice but not from knockout mice lacking functional serum and glucocorticoid inducible kinase SGK1. Thus, glucocorticoids indeed up-regulate Na+/K+ ATPase activity, an effect requiring SGK1.