| First Author | Boini KM | Year | 2006 |
| Journal | Diabetes | Volume | 55 |
| Issue | 7 | Pages | 2059-66 |
| PubMed ID | 16804076 | Mgi Jnum | J:111857 |
| Mgi Id | MGI:3654972 | Doi | 10.2337/db05-1038 |
| Citation | Boini KM, et al. (2006) Serum- and glucocorticoid-inducible kinase 1 mediates salt sensitivity of glucose tolerance. Diabetes 55(7):2059-66 |
| abstractText | 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. |
