Linked Life Data

21690090

Source:http://linkedlifedata.com/resource/pubmed/id/21690090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2011-8-22
pubmed:abstractText
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 virus X protein (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 for JNK in 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29872-81
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed-meshheading:21690090-Animals, pubmed-meshheading:21690090-Endothelium-Dependent Relaxing Factors, pubmed-meshheading:21690090-Gene Expression Regulation, Enzymologic, pubmed-meshheading:21690090-Gluconeogenesis, pubmed-meshheading:21690090-Glucose, pubmed-meshheading:21690090-Hep G2 Cells, pubmed-meshheading:21690090-Hepatitis B virus, pubmed-meshheading:21690090-Homeostasis, pubmed-meshheading:21690090-Humans, pubmed-meshheading:21690090-Hyperglycemia, pubmed-meshheading:21690090-Liver, pubmed-meshheading:21690090-Mice, pubmed-meshheading:21690090-Mice, Knockout, pubmed-meshheading:21690090-Mitogen-Activated Protein Kinase 8, pubmed-meshheading:21690090-Nitric Oxide, pubmed-meshheading:21690090-Nitric Oxide Synthase Type II, pubmed-meshheading:21690090-Signal Transduction, pubmed-meshheading:21690090-Trans-Activators
pubmed:year
2011
pubmed:articleTitle
Hepatitis B virus X protein regulates hepatic glucose homeostasis via activation of inducible nitric oxide synthase.
pubmed:affiliation
Disease Model Research Laboratory, Aging Research Center and World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural