Journal
BIOCHEMICAL JOURNAL
Volume 464, Issue -, Pages 281-289Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20141005
Keywords
db/db mice; extracellular-signal-regulated kinase 1/2 (ERK 1/2); glucose; hepatocyte; insulin signalling; liver; serum-and glucocorticoid-regulated kinase 1 (SGK 1)
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Funding
- National Natural Science Foundation [81130076, 81325005, 31271269, 81100615, 81390350]
- Ministry of Science and Technology of China [2010CB912502]
- Shanghai Science and Technology Commission [13JC1409000]
- International S&T Cooperation Program of China [Singapore] [2014DFG32470]
- Chinese Academy of Sciences
- National Institutes of Health [DK 41481, DK 58898]
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Insulin resistance is a major hallmark of metabolic syndromes, including Type 2 diabetes. Although numerous functions of SGK 1 (serum- and glucocorticoid-regulated kinase 1) have been identified, a direct effect of SGK 1 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-shERK 1/2-mediated inhibition of ERK1/2 reverses the attenuated insulin sensitivity in Ad-shSGK I mice. Finally, we found that SGK I functions are compromised under insulin-resistant conditions and overexpression of SGK I by Ad-SGK 1 significantly ameliorates insulin resistance in both glucosamine-treated HepG2 cells and livers of db/db mice, a genetic model of insulin resistance.
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