Intestinal function of gene-targeted mice lacking serum- and glucocorticoid-inducible kinase 1
| Autor: | Dietmar Kuhl, Florian Lang, Lothar Just, Ciprian D. Sandu, Peer Wulff, Florian Grahammer, Thomas Skutella, Guido Henke, Azeemudeen Hussain, Teut Risler, Björn Friedrich, Rexhep Rexhepaj, Marco Metzger |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Sodium-Hydrogen Exchangers Physiology Mice Transgenic Biology Protein Serine-Threonine Kinases Immediate-Early Proteins Mice Sodium-Glucose Transporter 1 Physiology (medical) Internal medicine medicine Animals Gene Cells Cultured Hepatology urogenital system Kinase Sodium-Hydrogen Exchanger 3 Gastroenterology Glucose transporter In vitro Intestines Endocrinology Gene Targeting SGK1 Cotransporter Glucocorticoid Function (biology) medicine.drug |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 290(6) |
| ISSN: | 0193-1857 |
| Popis: | 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 (ΔpHNHE) reflecting NHE activity. As a result, intestinal SGK1 transcript levels were significantly enhanced by a 4-day treatment with 10 μg·mg body wt−1·day−1 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. ΔpHNHE was similar in sgk1−/− and sgk1+/+ mice before treatment. Dex increased ΔpHNHE 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|