First Author | Liu H | Year | 2014 |
Journal | Biochem J | Volume | 464 |
Issue | 2 | Pages | 281-9 |
PubMed ID | 25222560 | Mgi Jnum | J:217818 |
Mgi Id | MGI:5615859 | Doi | 10.1042/BJ20141005 |
Citation | Liu H, et al. (2014) Hepatic serum- and glucocorticoid-regulated protein kinase 1 (SGK1) regulates insulin sensitivity in mice via extracellular-signal-regulated kinase 1/2 (ERK1/2). Biochem J 464(2):281-9 |
abstractText | Insulin resistance is a major hallmark of metabolic syndromes, including Type 2 diabetes. Although numerous functions of SGK1 (serum- and glucocorticoid-regulated kinase 1) have been identified, a direct effect of SGK1 on insulin sensitivity has not been previously reported. In the present study, we generated liver-specific SGK1-knockout mice and found that these mice developed glucose intolerance and insulin resistance. We also found that insulin signalling is enhanced or impaired in Hep1-6 cells infected with adenoviruses expressing SGK1 (Ad-SGK1) or shRNA directed against the coding region of SGK1 (Ad-shSGK1) respectively. In addition, we determined that SGK1 inhibits ERK1/2 (extracellular-signal-regulated kinase 1/2) activity in liver and Ad-shERK1/2-mediated inhibition of ERK1/2 reverses the attenuated insulin sensitivity in Ad-shSGK1 mice. Finally, we found that SGK1 functions are compromised under insulin-resistant conditions and overexpression of SGK1 by Ad-SGK1 significantly ameliorates insulin resistance in both glucosamine-treated HepG2 cells and livers of db/db mice, a genetic model of insulin resistance. |