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HORMONES AND SIGNALING
Departments of 1Physiology, 2Internal Medicine, and 3Anatomy, University of Tübingen, Tübingen; 4Department of Clinical Neurobiology, University of Heidelberg, Heidelberg; and 5Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Berlin, Germany
Submitted 23 May 2005 ; accepted in final form 4 January 2006
In vitro experiments have revealed the ability of serum- and glucocorticoid-inducible kinase 1 (SGK1) to stimulate intestinal Na+-coupled glucose cotransporter 1 (SGLT1) and intestinal Na+/H+ exchanger 3 (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 the 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·mg body wt1·day1 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 approximately threefold in sgk1+/+ mice but not in sgk1/ mice.
pHNHE was similar in sgk1/ and sgk1+/+ mice before treatment. Dex increased
pHNHE approximately threefold in sgk1+/+ mice and approximately twofold in sgk1/mice, an effect significantly blunted in the presence of the specific NHE3 blocker S-3226 (10 µM). According to Western blot analysis, Dex significantly enhanced SGLT1 and NHE3 protein abundance in brush-border membranes of sgk1+/+ mice but not of sgk1/mice. In conclusion, basic functions of SGLT1 and NHE3 in the intestine do not require stimulation by SGK1. However, the effects of glucocorticoids on SGLT1 are fully, and on NHE3 partially, dependent on SGK1.
glucocorticoids; glucose transport; Na+-coupled glucose transporter 1; Na+/H+ exchanger3; intestine
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