@article{oai:kanazawa-u.repo.nii.ac.jp:00014573,
 author = {Misu, Hirofumi and Takamura, Toshinari and Takayama, Hiroaki and Hayashi, Hiroto and Matsuzawa-Nagata, Naoto and Kurita, Seiichiro and Ishikura, Kazuhide and Ando, Hitoshi and Takeshita, Yumie and Ota, Tsuguhito and Sakurai, Masaru and Yamashita, Tatsuya and Mizukoshi, Eishiro and Yamashita, Taro and Honda, Masao and Miyamoto, Kenichi and Kubota, Tetsuya and Kubota, Naoto and Kadowaki, Takashi and Kim, Han-Jong and Lee, In-kyu and Minokoshi, Yasuhiko and Saito, Yoshiro and Takahashi, Kazuhiko and Yamada, Yoshihiro and Takakura, Nobuyuki and Kaneko, Shuichi},
 issue = {5},
 journal = {Cell Metabolism},
 month = {Nov},
 note = {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., 金沢大学医薬保健研究域医学系},
 pages = {483--495},
 title = {A liver-derived secretory protein, selenoprotein P, causes insulin resistance},
 volume = {12},
 year = {2010}
}