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.
Original language | English (US) |
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Pages (from-to) | 281-289 |
Number of pages | 9 |
Journal | Biochemical Journal |
Volume | 464 |
Issue number | 2 |
DOIs | |
State | Published - Dec 1 2014 |
Externally published | Yes |
Keywords
- Db/db mice
- Extracellular-signal-regulated kinase 1/2 (ERK1/2)
- Glucose
- Hepatocyte
- Insulin signalling
- Liver
- Serumand glucocorticoid-regulated kinase 1 (SGK1)
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology