Lipid-induced p62dok up-regulation enhances hepatic gluconeogenesis |
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Authors: | PEI Ya-ping DING You-ming |
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Affiliation: | 1. University Hospital, Hubei University of Chinese Medicine, Wuhan 430065, China;2. Department of Hepatobiliary & Laparoscopic Surgery, People's Hospital of Wuhan University, Wuhan 430060, China |
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Abstract: | AIM:To investigate the potential role of p62dok in the regulation of hepatic gluconeogenesis. METHODS:The expression of p62dok, insulin signaling transduction, and hepatic gluconeogenesis were investigated in the liver tissues of mice treated with high-fat diet(HFD) and in cultured mouse hepatocytes treated with free fatty acid(FFA). The experiments of gene silencing and overexpression were conducted to observe the effects of p62dok on insulin signal transduction and hepatic gluconeogenesis in cultured mouse hepatocytes. Western blotting was used to detect the protein levels and the phosphorylation statue. RESULTS:The increased p62dok levels were found in the liver tissues from HFD-treated mice and FFA-treated hepatocytes. Meanwhile, phosphorylation of Akt and forkhead box O1 protein(FoxO1) was were decreased and the expression of glucose-6-phosphatase(G6Pase) and phosphoenolpyruvate carboxykinase(PEPCK) was increased. Silencing of p62dok in cultured hepatocytes treated with FFA induced the increase in phosphorylation of Akt and FoxO1, and decrease in the protein levels of G6Pase and PEPCK. CONCLUSION:Up-regulation of p62dok induced by HFD or FFA enhances hepatic gluconeogenesis via inhibiting insulin signal transduction. |
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Keywords: | p62dok Hepatocytes Gluconeogenesis Insulin signal transduction |
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