A liver-derived secretory protein, selenoprotein P, causes insulin resistance

• Misu, Hirofumi

• Takamura, Toshinari

• Takayama, Hiroaki

• Hayashi, Hiroto

• Matsuzawa-Nagata, Naoto

• Kurita, Seiichiro

• Ishikura, Kazuhide

• Ando, Hitoshi

• Takeshita, Yumie

• Ota, Tsuguhito

• Sakurai, Masaru

• Yamashita, Tatsuya

• Mizukoshi, Eishiro

• Yamashita, Taro

• Honda, Masao

• Miyamoto, Kenichi

• Kubota, Tetsuya

• Kubota, Naoto

• Kadowaki, Takashi

• Kim, Han-Jong

• Lee, In-kyu

• Minokoshi, Yasuhiko

• Saito, Yoshiro

• Takahashi, Kazuhiko

• Yamada, Yoshihiro

• Takakura, Nobuyuki

• Kaneko, Shuichi

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

Details

• CRID: 1050001335953795712
• NII Article ID: 120002661942
• NII Book ID: AA11978571
• ISSN: 15504131
• Web Site: http://hdl.handle.net/2297/25782
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles
  • KAKEN