Ullrich Susanne, Zhang Ying, Avram Diana, Ranta Felicia, Kuhl Dietmar, Häring Hans-Ulrich, Lang Florian
Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
Biochem Biophys Res Commun. 2007 Jan 19;352(3):662-7. doi: 10.1016/j.bbrc.2006.11.065. Epub 2006 Nov 21.
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 beta-cells. The glucocorticoid dexamethasone (100 nmol/l for 1 day) significantly increased Na+/K+ ATPase alpha1/beta1-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 micromol/l). Dexamethasone (100 nmol/l) increased K+ current in beta-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.
糖皮质激素会抑制胰岛素释放,这种作用部分归因于钾离子通道的激活。与这些通道类似,钠钾ATP酶活性可使质膜复极化。本研究探讨了糖皮质激素是否会增加胰腺β细胞中的钠钾ATP酶活性。糖皮质激素地塞米松(100 nmol/l,作用1天)显著增加了INS-1细胞中钠钾ATP酶α1/β1亚基的转录水平以及反映钠钾ATP酶活性的哇巴因敏感外向电流,糖皮质激素受体阻滞剂RU487(1 μmol/l)可减弱这些作用。地塞米松(100 nmol/l)增加了野生型小鼠β细胞中的钾电流,但对缺乏功能性血清和糖皮质激素诱导激酶SGK1的基因敲除小鼠的β细胞则没有这种作用。因此,糖皮质激素确实会上调钠钾ATP酶活性,这一作用需要SGK1参与。