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- Title
Serum- and Glucocorticoid-Inducible Kinase 1 Mediates Salt Sensitivity of Glucose Tolerance.
- Authors
Boini, Krishna M.; Hennige, Anita M.; Huang, Dan Yang; Friedrich, Björn; Palmada, Monica; Boehmer, Christoph; Grahammer, Florian; Artunc, Ferruh; Ullrich, Susanne; Avram, Diana; Osswald, Hartmut; Wulff, Peer; Kuhl, Dietmar; Vallon, Volker; Häring, Hans-Ulrich; Lang, Florian
- Abstract
Excess salt intake decreases peripheral glucose uptake, thus impairing glucose tolerance. Stimulation of cellular glucose uptake involves phosphatidylinositide-3-kinase (PI-3K)-dependent activation of protein kinase B/Akt. A further kinase downstream of PI-3K is serum- and glucocorticoid-inducible kinase (SGK)1, which is upregulated by mineralocorticoids and, thus, downregulated by salt intake. To explore the role of SGK1 in salt-dependent glucose uptake, SGK1 knockout mice (sgk1-/-) and their wild-type littermates (sgk1+/+) were allowed free access to either tap water (control) or 1% saline (high salt). According to Western blotting, high salt decreased and deoxycorticosterone acetate (DOCA; 35 mg/kg body wt) increased SGK1 protein abundance in skeletal muscle and fat tissue of sgk1+/+ mice. Intraperitoneal injection of glucose (3 g/kg body wt) into sgk1+/+ mice transiently increased plasma glucose concentration approaching significantly higher values ([glucose]p,max) in high salt (281 ± 39 mg/dl) than in control (164 ± 23 mg/dl) animals. DOCA did not significantly modify [glucose]p,max in control sgk1+/+ mice but significantly decreased [glucose]p, max in high-salt sgk1+/+ mice, an effect reversed by spironolactone (50 mg/kg body wt). [Glucose]p,max was in sgk1-/- mice insensitive to high salt and significantly higher than in control sgk1+/+ mice. Uptake of 2-deoxy-D-[1,2-3]H]glucose into skeletal muscle and fat tissue was significantly smaller in sgk1-/- mice than in sgk1+/+ mice and decreased by high salt in sgk1+/+ mice. Transfection of HEK-293 cells with active S422DSGK1, but not inactive K127NSGK, stimulated phloretin-sensitive glucose uptake. In conclusion, high salt decreases SGK1-dependent cellular glucose uptake. SGK1 thus participates in the link between salt intake and glucose tolerance. Diabetes 55: 2059-2066, 2006
- Subjects
SALT in the body; GLUCOSE; GLUCOSE tolerance tests; PROTEIN kinases; METABOLISM
- Publication
Diabetes, 2006, Vol 55, Issue 7, p2059
- ISSN
0012-1797
- Publication type
Abstract
- DOI
10.2337/db05-1038