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- Title
Hepatic serum- and glucocorticoid-regulated protein kinase 1 (SGK1) regulates insulin sensitivity in mice via extracellular-signal-regulated kinase 1/2 (ERK1/2).
- Authors
Hao Liu; Junjie Yu; Tingting Xia; Yuzhong Xiao; Qian Zhang; Bin Liu; Yajie Guo; Jiali Deng; Yalan Deng; Shanghai Chen; Naray-Fejes-Toth, Aniko; Fejes-Toth, Geza; Feifan Guo
- Abstract
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 insulinresistant conditions and overexpression of SGK1 by Ad-SGK1 significantly ameliorates insulin resistance in both glucosaminetreated HepG2 cells and livers of db/db mice, a genetic model of insulin resistance.
- Subjects
TYPE 2 diabetes; CELLULAR signal transduction; LABORATORY mice; INSULIN resistance; SGK protein; LIVER cells
- Publication
Biochemical Journal, 2014, Vol 464, Issue 2, p281
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20141005