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Title 

Hepatitis B virus X protein regulates hepatic glucose homeostasis via activation of inducible nitric oxide synthase

Authors 

Hye Jun ShinYoung Ho ParkSun-Uk KimH B MoonD S ParkChul Ho LeeD S LeeI S SongD H LeeM KimNam-Soon KimD G KimJ M KimS K KimY N KimS S KimC S ChoiY B KimDae Yeul Yu

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2011

Citation 

Journal of Biological Chemistry, vol. 286, no. 34, pp. 29872-29881

Abstract 

Dysregulation of liver functions leads to insulin resistance causing type 2 diabetes mellitus and is often found in chronic liver diseases. However, the mechanisms of hepatic dysfunction leading to hepatic metabolic disorder are still poorly understood in chronic liver diseases. The current work investigated the role of hepatitis B virusXprotein (HBx) in regulating glucose metabolism. We studied HBx-overexpressing (HBxTg) mice and HBxTg mice lacking inducible nitric oxide synthase (iNOS). Here we show that gene expressions of the key gluconeogenic enzymes were significantly increased in HepG2 cells expressing HBx (HepG2-HBx) and in non-tumor liver tissues of hepatitis B virus patients with high levels of HBx expression. In the liver of HBxTg mice, the expressions of gluconeogenic genes were also elevated, leading to hyperglycemia by increasing hepatic glucose production. However, this effect was insufficient to cause systemic insulin resistance. Importantly, the actions of HBx on hepatic glucose metabolism are thought to be mediated via iNOS signaling, as evidenced by the fact that deficiency of iNOS restored HBx-induced hyperglycemia by suppressing the gene expression of gluconeogenic enzymes. Treatment of HepG2-HBx cells with nitric oxide (NO) caused a significant increase in the expression of gluconeogenic genes, but JNK1 inhibition was completely normalized. Furthermore, hyperactivation of JNK1 in the liver of HBxTg mice was also suppressed in the absence of iNOS, indicating the critical role forJNKin the mutual regulation of HBx-and iNOS-mediated glucose metabolism. These findings establish a novel mechanism of HBx-driven hepatic metabolic disorder that is modulated by iNOS-mediated activation of JNK.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M111.259978

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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