Role of the prolyl isomerase Pin1 in diabetes

• Project/Area Number: 20790648
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: NAKATSU Yusuke Hiroshima University, 医歯薬学総合研究科, 助教 (20452584)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Pin1 / IRS-1 / インスリンシグナル / KOマウス / ob / obマウス / 糖尿病 / 糖新生系 / CRTC2 / インスリン

Research Abstract

We identified prolyl isomerase Pin1 as IRS-1 binding protein. Pin1 overexpression enhanced insulin signaling, while pin1 knockdown suppressed. In addition, overexpression of Pin1 in ob/ob mouse liver elevated IRS-1 mediating insulin signaling, while Pin1 KO mouse exhibited insulin resistance and glucose intolerance. Taking all of these results together, we conclude that Pin1 plays an important role in the enhancement of IRS-1 mediating insulin actions.

Research Products

• [Journal Article] Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy (2010)
  • Author(s): Cui X, Kushiyama A, Yoneda M, Nakatsu Y, (著者19人)
  • Journal Title: Diabetes Res Clin Pract 87(1) Pages: 57-63
  • Peer Reviewed
• [Journal Article] Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy (2010)
  • Author(s): Cui X, Kushiyama A, Yoneda M, Nakatsu Y, Guo Y, Zhang J, Ono H, Kanna M, Sakoda H, Ono H, Kikuchi T, Fujishiro M, Shiomi M, Kamata H, Kurihara H, Kikuchi M, Kawazu S, Nishimura F, Asano T
  • Journal Title: Diabetes Res Clin Pract. 87 Pages: 57-63
  • Peer Reviewed
• [Journal Article] Decreased SIRT1 expression and LKB1 phosphorylation occur with long-term high-fat diet feeding, in addition to AMPK phosphorylation impairment in the early phase (2010)
  • Author(s): Yoneda M., Guo Y., Ono H., Nakatsu Y., Zhang J., Cui X., Iwashita M., Kumamoto S., Tsuchiya Y., Sakoda H., Fujishiro M, Kushiyama A., Koketsu Y., Kikuchi T., Kamata H., Nishimura F., Asano T.
  • Journal Title: Obesity Res Clin Pract (In press)
  • Peer Reviewed
• [Journal Article] Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate (2009)
  • Author(s): Nakatsu Y, Kotake Y, Takishita T, Ohta S
  • Journal Title: Toxicol Appl Pharmacol 240(2) Pages: 292-298
  • Peer Reviewed
• [Journal Article] Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate (2009)
  • Author(s): Nakatsu Y, Kotake Y, Takishita T, Ohta S.
  • Journal Title: Toxicol Appl Pharmacol 240 Pages: 292-298
  • Peer Reviewed
• [Journal Article] Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells (2008)
  • Author(s): Egawa M, Kamata H, Kushiyama A, Sakoda H, Fujishiro M, Horike N, Yoneda M, Nakatsu Y, (著者14人)
  • Journal Title: Placenta 29(12) Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death (2008)
  • Author(s): Nakatsu Y, Kotake Y, Hino A, Ohta S
  • Journal Title: Toxicol Appl Pharmacol 230(3) Pages: 358-363
  • Peer Reviewed
• [Presentation] プロリル異性化酵素Pin1はTORC2と結合しCRE活性を抑制することで、肝の糖新生系を制御する (2009)
  • Author(s): 中津祐介、堀家なな緒、櫛山暁史、迫田秀之、大野晴也、神名真智、鎌田英明、栗原裕基、内田隆史、浅野知一郎
  • Organizer: 生化学会2009
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-26
• [Presentation] プロリル異性化酵素Pin1はTORC2と結合しCRE活性を抑制することで、肝の糖新生系を制御する (2009)
  • Author(s): 中津祐介
  • Organizer: 生化学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-23
• [Presentation] Pin1 binds to IRS-1, and functions as a nutrient-sensing enhancer of insulin signaling (2009)
  • Author(s): Yusuke Nakatsu
  • Organizer: アメリカ糖尿病学会
  • Place of Presentation: アメリカ
  • Year and Date: 2009-06-25
• [Presentation] Pin1 binds to IRS-1, and functions as a nutrient-sensing enhancer of insulin signaling (2009)
  • Author(s): Yusuke Nakatsu, Hideyuki Sakoda, Akifumi Kushiyama, Midori Fujishiro, Masayasu Yoneda, Haruya Ohno, Hideaki Kamata, Takafumi Uchida, Tomoichiro Asano
  • Organizer: 第69回アメリカ糖尿病学会
  • Place of Presentation: アメリカルイジアナ州ニューホリンズ
  • Year and Date: 2009-06-03
• [Presentation] Pin1はIRS-1と結合し、インスリンシグナルを促進する (2009)
  • Author(s): 中津祐介
  • Organizer: 第52回日本糖尿病学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-21
• [Presentation] プロリン異性化酵素Pin1はIRS-1のSer/Pro配列を認識し、結合する (2008)
  • Author(s): 中津祐介
  • Organizer: 第81回日本生化学会・分子生物学会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-15
• [Presentation] プロリン異性化酵素Pin1はIRS-1のSer/Pro配列を認識し、結合する (2008)
  • Author(s): 中津祐介
  • Organizer: 生化学・分子生物学合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11