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Abstract

金沢大学医薬保健研究域医学系The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secretory proteins, termed hepatokines. Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance. Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans. Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice. The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate-activated protein kinase (AMPK). In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes. © 2010 Elsevier Inc.

Journal

  • Cell Metabolism

    Cell Metabolism 12(5), 483-495, 2010-11-03

    Elsevier

Cited by:  6

Codes

  • NII Article ID (NAID)
    120002661942
  • NII NACSIS-CAT ID (NCID)
    AA11978571
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    1550-4131
  • Data Source
    CJPref  IR 
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