Investigation of the role of insulin signaling molecules on development of hepatocytes into hepatocytes with fatty changes

• Project/Area Number: 22790847
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: FUJISHIRO Midori 東京大学, 医学部附属病院, 助教 (50420211)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: エネルギー / 糖質代謝異常 / 高グルコース刺激 / インスリン抵抗性 / インスリン受容体

Research Abstract

We have found that chronic hyperglycemia induced marked increase of insulin receptor expression in the liver cells. I investigated if the mechanism of this change involved in a vicious cycle of hepatic insulin resistance. First, I analyzed protein expression levels of transcription factors predicted to bind with insulin receptor promoter regions and their cofactors of the various insulin acting organs with chronic high glucose stimulation, but could not identify the protein that changed its expression levels during such stimulation. Now I am further analyzing the changes during chronically high glucose stimulation with hyperinsulinemia

Research Products

• [Journal Article] LST8 level controls basal p70 S6 kinase and Akt phosphorylations, and mTORC1 and mTORC2 negatively regulate each other by competing for association with LST8. (2012)
  • Author(s): Kikuchi T, Zhang J, Sakoda H, Koketsu Y, Fujishiro M, Kushiyama A, Nakatsu Y, Kamata H, Inoki K, Takahashi S, Kurihara H, Hideki K, Oka Y, Asano T
  • Journal Title: Obesity Research and Clinical Practice Volume: 6 Issue: 3 Pages: 175-262
  • DOI: 10.1016/j.orcp.2011.10.002
  • Peer Reviewed
• [Journal Article] Xanthine Oxidoreductase Is Involved in Macrophage Foam Cell Formation and atherosclerosis development (2012)
  • Author(s): Kushiyama A, Okubo H, Sakoda H, Kikuchi T, Fujishiro M, Sato H, Kushiyama S, Iwashita M, Nishimura F, Fukushima T, Nakatsu Y, Kamata H, Kawazu S, Higashi Y, Kurihara H, Asano T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Issue: 2 Pages: 291-298
  • DOI: 10.1161/atvbaha.111.234559
  • Peer Reviewed
• [Journal Article] Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. (2012)
  • Author(s): Iwashita M, Sakoda H, Kushiyama A, Fujishiro M, Ohno H, Nakatsu Y, Fukushima T, Kumamoto S, Tsuchiya Y, Kikuchi T, Kurihara H, Akazawa H, Komuro I, Kamata H, Nishimura F, Asano T.
  • Journal Title: American Journal of Physiology - Endocrinology and Metabolism Volume: 302 Issue: 3 Pages: 286-296
  • DOI: 10.1152/ajpendo.00324.2011
  • Peer Reviewed
• [Journal Article] Xanthine oxidoreductase is involved in macrophage foam cell formation and athe rosclerosis development (2012)
  • Author(s): Kushiyama A, Fujishiro M, et al
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32(2) Pages: 291-298
  • Peer Reviewed
• [Journal Article] Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes (2012)
  • Author(s): Iwashita M, Fujishiro M, et al
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 302(3)
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Issue: 23 Pages: 20812-20822
  • DOI: 10.1074/jbc.m110.206904
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Otani Y, Okubo H, Yoneda M, Fukushima T, Kamata H, Nishimura F, Kurihara H, Katagiri H, Oka Y, Asano T
  • Journal Title: Am J Physiol Cell Physiol Volume: 300(5) Issue: 5 Pages: 1047-54
  • DOI: 10.1152/ajpcell.00416.2010
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Fujishiro M, et al
  • Journal Title: Am J Physiol Cell Physiol Volume: 300(5)
  • Peer Reviewed
• [Journal Article] LST8levelcontrolsbasalp70 S6 kinase and Akt phosphorylations, and mTORC1 and mTORC2 negatively regulate each other by competing for association with LST8
  • Author(s): Kikuchi T, Fujishiro M, et al
  • Journal Title: Obesity Research & Clinical Practice Volume: (In Press)
  • Peer Reviewed
• [Presentation] 長時間高グルコース刺激による肝細胞内インスリン受容体遺伝子発現調節機構の解明 (2010)
  • Author(s): 藤城緑
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山市デジタルミュージアム(岡山県)
  • Year and Date: 2010-05-28