Liver producing hormones and life style related diseases

• Project/Area Number: 23249042
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: KANEKO Shuichi 金沢大学, 医学系, 教授 (60185923)
• Co-Investigator(Kenkyū-buntansha): TAKAMURA Toshinari 金沢大学, 医学系, 教授 (00324111) ; HONDA Masao 金沢大学, 保健学系, 教授 (00272980)
• Project Period (FY): 2011-05-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000); Fiscal Year 2013: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2012: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000); Fiscal Year 2011: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
• Keywords: ゲノム / 発現制御 / 肝臓 / 栄養 / 生活習慣病

Research Abstract

Influence of liver producing hormones, termed as hepatokine, on life style diseases such as diabetes were studied. Selenoprotein P was published as the first hepatokine in Cell Metabolism 2010 from our laboratory. Selenoprotein P induces insulin resistance coordinated with adipose and muscle tissues (published in Pros One 2012, and 2014, respectively). Expression of Selenoprotein was decreased by the treatment of metformin (J Biol Chem 2014). Another hepatokine, leukocyte cell-derived chemotaxin 2, was newly identified (Diabetes 2014).

Research Products

• [Journal Article] LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance (2014)
  • Author(s): F Lan, H Misu, K Chikamoto, H Takayama, A Kikuchi, K Mohri, N Takata, H Hayashi, N Matsuzawa-Nagata, Y Takeshita, H Noda, Y Matsumoto, T Ota, T Nagano, M Nakagen, KI Miyamoto, K Takatsuki, T Seo, K Iwayama, K Tokuyama, S Matsugo, H Tang, Y Saito, S Yamagoe, S Kaneko, T Takamura
  • Journal Title: Diabetes Volume: (in press)
  • NAID: 120005440333
• [Journal Article] The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism : a randomised controlled trial (2014)
  • Author(s): Y Takeshita, T Takamura, M Honda, Y Kita, Y Zen, KI Kato, H Misu, T Ota, M Nakamura, K Yamada, H Sunagozaka, K Arai, T Yamashita, E Mizukoshi, S Kaneko
  • Journal Title: Diabetologia Volume: 57(5) Issue: 5 Pages: 878-90
  • DOI: 10.1007/s00125-013-3149-9
  • Peer Reviewed / Open Access
• [Journal Article] Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic Fatty liver disease (2014)
  • Author(s): K Kato, T Takamura, Y Takeshita, Y Ryu, H Misu, T Ota, K Tokuyama, S Nagasaka, M Matsuhisa, O Matsui, S Kaneko
  • Journal Title: PLoS One Volume: 9(3) Issue: 3 Pages: e92170-e92170
  • DOI: 10.1371/journal.pone.0092170
  • NAID: 120005440398
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis C patients with different interleukin 28B genotypes (2014)
  • Author(s): M Honda, T Shirasaki, T Shimakami, A Sakai, R Horii, K Arai, T Yamashita, Y Sakai, T Yamashita, H Okada, K Murai, M Nakamura, E Mizukoshi, S Kaneko
  • Journal Title: Hepatology Volume: 59(3) Issue: 3 Pages: 828-38
  • DOI: 10.1002/hep.26788
  • NAID: 120005447749
  • Peer Reviewed / Open Access
• [Journal Article] Metformin Suppresses Expression of the Selenoprotein P gene via an AMPK-FoxO3a Pathway in H4IIEC3 Hepatocytes (2014)
  • Author(s): H Takayama, H Misu, H Iwama, K Chikamoto, Y Saito, K Murao, A Teraguchi, F Lan, A Kikuchi, R Saito, N Tajima, T Shirasaki, S Matsugo, KI Miyamoto, S Kaneko, T Takamura
  • Journal Title: J Biol Chem Volume: 289(1) Issue: 1 Pages: 335-45
  • DOI: 10.1074/jbc.m113.479386
  • Peer Reviewed
• [Journal Article] LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. (2014)
  • Author(s): F Lan
  • Journal Title: Diabetes Volume: in press
  • Peer Reviewed
• [Journal Article] Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model (2013)
  • Author(s): A Seki, S Y akai, T Komura, A Nasti, K Yoshida, M Higashimoto, M Honda, S Usui, M Takamura, T Takamura, T Ochiya, K Furuichi, T Wada, S Kaneko
  • Journal Title: Hepatology Volume: 58(3) Issue: 3 Pages: 1133-42
  • DOI: 10.1002/hep.26470
  • Peer Reviewed
• [Journal Article] Discrete nature of EpCAM(+) and CD90(+) cancer stem cells in human hepatocellular carcinoma. (2013)
  • Author(s): Yamashita T, Nakamoto Y, et al.
  • Journal Title: Hepatology Volume: 57 Issue: 4 Pages: 1484-1497
  • DOI: 10.1002/hep.26168
  • Peer Reviewed
• [Journal Article] Dosing time-dependent effect of raloxifene on plasma plasminogen activator inhibitor-1 concentrations in post-menopausal women with osteoporosis (2013)
  • Author(s): H Ando, T Otoda, H Ookami, Y Nagai, A Inano, T Takamura, K Ushijima, K Hosohata, E Matsushita, T Saito, S Kaneko, A Fujimura
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 40(3) Issue: 3 Pages: 227-32
  • DOI: 10.1111/1440-1681.12055
  • Peer Reviewed
• [Journal Article] Proteasome dysfunction mediates obesity-induced endoplasmic reticulum stress and insulin resistance in the liver (2013)
  • Author(s): T Otoda, T Takamura, H Misu, T Ota, S Murata, H Hayashi, H Takayama, A Kikuchi, T Kanamori, KR Shima, F Lan, T Takeda, S Kurita, K Ishikura, Y Kita, K Iwayama, KI Kato, M Uno, Y Takeshita, M Yamamoto, K Tokuyama, S Iseki, K Tanaka, S Kaneko
  • Journal Title: Diabetes Volume: 62(3) Issue: 3 Pages: 811-24
  • DOI: 10.2337/db11-1652
  • Peer Reviewed
• [Journal Article] Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance : Implications for type 2 diabetes. Metabolism (2012)
  • Author(s): Honda M, (他12名, 12番目)
  • Journal Title: Epub ahead of print Volume: (Epub ahead of print) Issue: 10 Pages: 1388-94
  • DOI: 10.1016/j.metabol.2012.03.011
  • Peer Reviewed
• [Journal Article] Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis (2012)
  • Author(s): Y Kita, T Takamura, H Misu, T Ota, S Kurita, Y Takeshita, M Uno, N Matsuzawa-Nagata, K Kato, H Ando, A Fujimura, K Hayashi, T Kimura, Y Ni, T Otoda, K Miyamoto, Y Zen, Y Nakanuma, S Kaneko
  • Journal Title: PLoS One Volume: 7(9) Issue: 9 Pages: e43056-e43056
  • DOI: 10.1371/journal.pone.0043056
  • NAID: 120004966626
  • Peer Reviewed
• [Journal Article] Fatty liver as a consequence and cause of insulin resistance : Lessons from type 2 diabetic liver (2012)
  • Author(s): T Takamura, H Misu, T Ota, S Kaneko
  • Journal Title: Endocr J Volume: 59(9) Pages: 745-63
  • NAID: 10031123118
• [Journal Article] CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status (2012)
  • Author(s): Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, Takamura T, Yamamoto H, Miyamoto K, Ginsberg HN, Mukaida N, Kaneko S, Ota T
  • Journal Title: Diabetes IN PRESS Volume: 61(7) Issue: 7 Pages: 1680-90
  • DOI: 10.2337/db11-1506
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of insulin aspart in patients with Type 2 diabetes : Assessment using a meal tolerance test under clinical conditions (2012)
  • Author(s): H Ando, S Kurita, A Shimizu, K Kato, K Ishikura, K Taji, M Uno, Y Takeshita, H Misu, A Fujimura, S Kaneko, T Takamura
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 39(6) Issue: 6 Pages: 528-34
  • DOI: 10.1111/j.1440-1681.2012.05708.x
  • NAID: 120004442389
  • Peer Reviewed
• [Journal Article] Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes (2012)
  • Author(s): H Misu, K Ishikura, S Kurita, Y Takeshita, T Ota, Y Saito, K Takahashi, S Kaneko, T Takamura
  • Journal Title: PLoS One Volume: 7(4) Issue: 4 Pages: e34952-e34952
  • DOI: 10.1371/journal.pone.0034952
  • NAID: 120004140847
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress inhibits STAT3-dependent suppression of hepatic gluconeogenesis via dephosphorylation and deacetylation (2012)
  • Author(s): Kimura K, Yamada T, Matsumoto M, Kasuga M, Inoue H., 他9名
  • Journal Title: Diabetes Volume: 61 Issue: 1 Pages: 61-73
  • DOI: 10.2337/db10-1684
  • Peer Reviewed
• [Journal Article] Dietary glycemic index and risk of type 2 diabetes in middle-aged Japanese men (2012)
  • Author(s): M Sakurai, K Nakamura, K Miura, T Takamura, K Yoshita, Y Morikawa, M Ishizaki, T Kido, Y Naruse, Y Suwazono, S Kaneko, S Sasaki, H Nakagawa
  • Journal Title: Metabolism Volume: 61(1) Issue: 12 Pages: 47-55
  • DOI: 10.1016/j.jada.2010.09.014
  • Peer Reviewed
• [Journal Article] Fatty liver as a consequence and cause of insulin resistance: Lessons from type 2 diabetic liver. (2012)
  • Author(s): T Takamura
  • Journal Title: Endocr J Volume: 59 Pages: 745-763
  • NAID: 10031123118
  • Peer Reviewed
• [Journal Article] CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status (2012)
  • Author(s): H Kitade
  • Journal Title: Diabetes Volume: (in press)
  • Peer Reviewed
• [Remarks]
  • URL: http://m-kanazawa.jp/
• [Remarks] 金沢大学附属病院内科（旧第一内科）恒常性制御学講座
  • URL: http://m-kanazawa.jp/
• [Remarks] 金沢大学医学部付属病院内科(旧第一内科)恒常性制御学講座
  • URL: http://www.m-kanazawa.jp/
• [Remarks]
  • URL: http://m-kanazawa.jp/