Submitted on May 23, 2005
Accepted on January 4, 2006
Intestinal function of gene targeted mice lacking the Serum and Glucocorticoid inducible kinase SGK1
Florian Grahammer1, Guido Henke1, Ciprian Sandu1, Rexhep Rexhepaj1, Azeemudeen Hussain1, Bjorn Friedrich2, Teut Risler2, Lothar Just3, Thomas Skutella3, Peer Wulff4, Dietmar Kuhl5, and Florian Lang1*
1 Department of Physiology, University of Tubingen, Tubingen, Germany
2 Department of Internal Medicine, University of Tubingen, Tubingen, Germany
3 Department of Anatomy, University of Tubingen, Tubingen, Germany
4 Department of Clinical Neurobiology, University of Heidelberg, Heidelberg, Germany
5 Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: florian.lang{at}uni-tuebingen.de.
In vitro experiments revealed the ability of the serum- and glucocorticoid-inducible kinase 1 (SGK1) to stimulate the intestinal Na+, glucose cotransporter SGLT1 and the intestinal Na+/H+ exchanger NHE3. The present study explored the contribution of SGK1 to the regulation of intestinal transport in vivo. SGK1 transcript levels were determined by real-time PCR and glucose induced currents (Ig), reflecting SGLT1 activity by Ussing chamber experiments. BCECF fluorescence was utilized for determination of Na+-dependent pH recovery from an ammonium pulse (
pHnhe) reflecting NHE activity. As a result, intestinal SGK1 transcript levels were significantly enhanced by a 4 day treatment with 10 µg/g BW/day dexamethasone (DEX). Ig was under control conditions virtually identical in SGK1-knockout mice (sgk1-/-) and their wild type littermates (sgk1+/+). A 4 day treatment with DEX, however, increased Ig ~3 fold in sgk1+/+ but not in sgk1-/- mice. pHnhe was similar in sgk1-/- and sgk1+/+ mice prior to treatment. DEX increased pHnhe ~3 fold in sgk1+/+ and ~2 fold in sgk1-/- mice, an effect significantly blunted in the presence of the specific NHE3 blocker S3226 (10 µM). According to Western blotting, DEX significantly enhanced SGLT1 and NHE3 protein abundance in brush border membranes of sgk1+/+ but not of sgk1-/- mice. In conclusion, basic functions of SGLT1 and NHE3 in intestine do not require stimulation by SGK1. However, the effects of glucocorticoids on SGLT1 are fully, and on NHE3 partially dependent on SGK1.
