Serum- and Glucocorticoid-Inducible Kinase 1 Mediates Salt Sensitivity of Glucose Tolerance
| Autor: | Florian Lang, Björn Friedrich, Hans-Ulrich Häring, Monica Palmada, Dietmar Kuhl, Florian Grahammer, Ferruh Artunc, Dan Yang Huang, Hartmut Osswald, Anita M. Hennige, Volker Vallon, Diana Avram, Krishna M. Boini, Susanne Ullrich, Christoph Boehmer, Peer Wulff |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Glucose uptake Intraperitoneal injection Protein Serine-Threonine Kinases Spironolactone Biology Immediate-Early Proteins Mice Phosphatidylinositol 3-Kinases Insulin resistance Internal medicine Internal Medicine medicine Animals Salt intake Desoxycorticosterone Protein kinase B Mice Knockout Sex Characteristics urogenital system Skeletal muscle medicine.disease Endocrinology medicine.anatomical_structure Organ Specificity SGK1 Female Glucocorticoid medicine.drug |
| Zdroj: | Diabetes. 55:2059-2066 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db05-1038 |
| Popis: | 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 (S422D)SGK1, but not inactive (K127N)SGK, 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. |
| Databáze: | OpenAIRE |
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