ヘパトカインを介した肝臓による恒常性維持機構の解明
御簾 博文Hirofumi Misu
所属機関 |
金沢大学 |
所属学部・学科など |
医薬保健研究域医学系 |
役職 |
准教授 |
研究課題概要
これまでに肥満症や2型糖尿病の病態に関連した肝臓由来分泌タンパクを同定し、これら機能未知の肝由来分泌タンパクを“ヘパトカイン"と呼ぶことを提唱してきました。本研究では、同定したヘパトカインの全身での多面的な作用を解明しその受容体を同定することで、ヘパトカインを標的とした過栄養関連疾患に対する新たな診断・治療法の開発を目指します。
成果
- H. Misu*, H. Takayama, Y. Saito, Y. Mita, A. Kikuchi, K. A. Ishii, K. Chikamoto, T. Kanamori, N. Tajima, F. Lan, Y. Takeshita, M. Honda, M. Tanaka, S. Kato, N. Matsuyama, Y. Yoshioka, K. Iwayama, K. Tokuyama, N. Akazawa, S. Maeda, K. Takekoshi, S. Matsugo, N. Noguchi, S. Kaneko and T. Takamura*. Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle. Nature Medicine 2017 23 508-516 *Co-corresponding author
- Y. Mita, K. Nakayama, S. Inari, Y. Nishito, Y. Yoshioka, N. Sakai, K. Sotani, T. Nagamura, Y. Kuzuhara, K. Inagaki, M. Iwasaki, H. Misu, M. Ikegawa, T. Takamura, N. Noguchi and Y. Saito. Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models. Nature Communications 2017 8(1) 1658
- K. Chikamoto, H. Misu*, H. Takayama, A. Kikuchi, K. A. Ishii, F. Lan, N. Takata, N. Tajima-Shirasaki, Y. Takeshita, H. Tsugane, S. Kaneko, S. Matsugo and T. Takamura*. Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice Biochem Biophys Res Commun 2016 478 1310-1316
*Co-corresponding author
- M. Tanaka, Y. Saito, H. Misu, S. Kato, Y. Kita, Y. Takeshita, T. Kanamori, T. Nagano, M. Nakagen, T. Urabe, T. Takamura, S. Kaneko, K. Takahashi and N. Matsuyama. Development of a Sol Particle Homogeneous Immunoassay for Measuring Full-Length Selenoprotein P in Human Serum J Clin Lab Anal 2016 30 114-122
- N. Tajima-Shirasaki, K. A. Ishii, H. Takayama, T. Shirasaki, H. Iwama, K. Chikamoto, Y. Saito, Y. Iwasaki, A. Teraguchi, F. Lan, A. Kikuchi, Y. Takeshita, K. Murao, S. Matsugo, S. Kaneko, H. Misu and T. Takamura. Eicosapentaenoic acid down-regulates expression of the selenoprotein P gene by inhibiting SREBP-1c protein independently of the AMP-activated protein kinase pathway in H4IIEC3 hepatocytes J Biol Chem 2017 292 10791-10800