Exploring a novel therapeutic strategy for obesity-induced diabetes by suppressing Class IB PI3-kinase activity

• Project/Area Number: 21390278
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: UEKI Kohjiro 東京大学, 医学部附属病院, 准教授 (00396714)
• Co-Investigator(Renkei-kenkyūsha): KADOWAKI Takashi 東京大学, 医学部・附属病院, 教授 (30185889)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: メタボリックシンドローム / 糖尿病 / 炎症

Research Abstract

Obesity initiates macrophage infiltration into adipose tissue and subsequent increased production of proinflammatory adipokines, leading to insulin resistance and diabetes. In this study, we test whether inhibition of Class 1B PI3 kinase(PI3K_γ) which is essential for macrophage chemotaxis, could ameliorate obesity-induced diabetes, by using PI3K_γknockout mice and a PI3K_γinhibitor, and assess the possibility that this strategy could be a novel therapeutic method for diabetes treatment

Research Products

• [Journal Article] Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage妖erived IL-6 dependent pathway (2011)
  • Author(s): Awazawa M, Ueki K, Yamauchi T, Kubota, Kadowaki T
  • Journal Title: Cell Metabolism Volume: 13 Issue: 4 Pages: 401-412
  • DOI: 10.1016/j.cmet.2011.02.010
  • Peer Reviewed
• [Journal Article] Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance (2011)
  • Author(s): Kobayashi N, Ueki K, Okazaki Y, Iwane A, Kubota N, Ohsugi M, Awazawa M, Kobayashi M, Sasako T, Kaneko K, Suzuki M, Nishikawa Y, Hara K, Yoshimura K, Koshima I, Goyama s, Murakami K, Sasaki J, Nagai R, Kurokawa M, Sasaki T, Kadowaki T
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 14 Pages: 5753-5758
  • DOI: 10.1073/pnas.1016430108
  • Peer Reviewed
• [Journal Article] Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1 (2010)
  • Author(s): Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., Ogata, H., Kubota, N.,Takamoto, I., Hayashi, YK., Yamauchi, N., Waki, H., Fukayama, M., Nishino, I., Tokuyama, K., Ueki, K., Oike, Y., Ishii, S., Hirose, K., Shimizu, T., Touhara, K., and Kadowaki, T
  • Journal Title: Nature Volume: 464 Issue: 7293 Pages: 1313-1319
  • DOI: 10.1038/nature08991
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor gamma agonist rosiglitazone increases expression of very low density lipoprotein receptor gene in adipocytes (2009)
  • Author(s): Takazawa T, Yamauchi T, Tsuchida A, Takata M, Hada Y, Iwabu M, Okada-Iwabu M, Ueki K and Kadowaki T
  • Journal Title: J Biol Chem Volume: 284 Issue: 44 Pages: 30049-30057
  • DOI: 10.1074/jbc.m109.047993
  • Peer Reviewed
• [Journal Article] CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity (2009)
  • Author(s): Nishimura S, Hara K, Ueki K, Kadowaki T
  • Journal Title: Nature Medicine Volume: 15 Issue: 8 Pages: 914-920
  • DOI: 10.1038/nm.1964
  • Peer Reviewed
• [Presentation] 脂肪組織における急性炎症経路と慢性炎症経路によるインスリン感受性の調節 (2012)
  • Author(s): 植木浩二郎
  • Organizer: 第26回日本糖尿病・肥満動物学会年次学術集会(シンポジウム)
  • Place of Presentation: 名古屋
  • Year and Date: 2012-02-17
• [Presentation] 脂肪組織における急性炎症経路と慢性炎症経路によるインスリン感受性の調節 (2012)
  • Author(s): 植木浩二郎
  • Organizer: 第26回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 名古屋(招待講演)
  • Year and Date: 2012-02-17
• [Presentation] インスリン抵抗性の分子基盤 (2011)
  • Author(s): 植木浩二郎
  • Organizer: 第32回日本肥満学会(教育講演)
  • Place of Presentation: 淡路島
  • Year and Date: 2011-09-23
• [Presentation] インスリン抵抗性の分子基盤 (2011)
  • Author(s): 植木浩二郎
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路島(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] 生理的一過性および慢性持続性ストレス経路によるインスリン感受性の制御機構 (2011)
  • Author(s): 植木浩二郎
  • Organizer: 第84回日本生化学会大会(シンポジウム)
  • Place of Presentation: 京都
  • Year and Date: 2011-09-21
• [Presentation] 生理的一過性および慢性持続性ストレス経路によるインスリン感受性の制御機構 (2011)
  • Author(s): 植木浩二郎
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-09-21
• [Presentation] Inflammatory response and insulin sensitivity (2011)
  • Author(s): Kohjiro Ueki
  • Organizer: The 2011 Seoul Symposium on Obesity and Diabetes(Symposium)
  • Place of Presentation: 韓国・ソウル
  • Year and Date: 2011-04-09
• [Presentation] Inflammatory response and insulin sensitivity (2011)
  • Author(s): 植木浩二郎
  • Organizer: The 2011 Seoul Symposium on Obesity and Diabetes
  • Place of Presentation: ソウル(韓国)(招待講演)
  • Year and Date: 2011-04-09
• [Presentation] Insulin resistance and NASH/NAFLD (2010)
  • Author(s): Kohjiro Ueki
  • Organizer: The 9th JSH single topic conference(Symposium)
  • Place of Presentation: 東京
  • Year and Date: 2010-11-18
• [Presentation] Insulin resistance and NASH/NAFLD (2010)
  • Author(s): 植木浩二郎
  • Organizer: The 9^<th> JSH single topic conference
  • Place of Presentation: 東京都
  • Year and Date: 2010-11-18
• [Presentation] Regulation of insulin sensitivity through changes in expression of adipokines by obesity (2010)
  • Author(s): 植木浩二郎
  • Organizer: シンポジウム
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] Regulation of insulin sensitivity through changes in expression of adipokines by obesity (2010)
  • Author(s): 植木浩二郎
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山市
  • Year and Date: 2010-05-28
• [Presentation] Class 1B PI3キナーゼ制御による肥満糖尿病治療の可能性の検討割 (2009)
  • Author(s): 植木浩二郎
  • Organizer: 第82回日本生化学会大会(シンポジウム)
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] Class 1B PI3キナーゼ制御による肥満糖尿病治療の可能性の検討割 (2009)
  • Author(s): 植木浩二郎、小林直樹、門脇孝
  • Organizer: 第82回日本生化学会大会シンポジウム(招待)
  • Place of Presentation: 神戸市
  • Year and Date: 2009-10-21
• [Presentation] Class 1B PI3キナーゼ制御による肥満糖尿病治療の可能性の検討割 (2009)
  • Author(s): 植木浩二郎
  • Organizer: 第30回日本肥満学会(シンポジウム)
  • Place of Presentation: 浜松
  • Year and Date: 2009-10-09
• [Presentation] Class 1B PI3キナーゼ制御による肥満糖尿病治療の可能性の検討割 (2009)
  • Author(s): 植木浩二郎、小林直樹、門脇孝
  • Organizer: 第30回日本肥満学会シンポジウム(招待)
  • Place of Presentation: 浜松市
  • Year and Date: 2009-10-09
• [Presentation] Class 1B PI3キナーゼ制御による肥満糖尿病治療の可能性の検討割 (2009)
  • Author(s): 植木浩二郎
  • Organizer: 第52回日本糖尿病学会年次学術集会(シンポジウム)
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-22
• [Presentation] Class 1B PI3キナーゼ制御による肥満糖尿病治療の可能性の検討割 (2009)
  • Author(s): 植木浩二郎、小林直樹、門脇孝
  • Organizer: 第52回日本糖尿病学会年次学術集会シンポジウム(招待)
  • Place of Presentation: 大阪市
  • Year and Date: 2009-05-22
• [Presentation] 肥満糖尿病におけるClass IB PI3キナーゼの役割 (2009)
  • Author(s): 植木浩二郎
  • Organizer: 82回日本内分泌学会学術総会(シンポジウム)
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-23
• [Presentation] 肥満糖尿病におけるClass IB PI3キナーゼの役割 (2009)
  • Author(s): 植木浩二郎、小林直樹、門脇孝
  • Organizer: 第82回日本内分泌学会学術総会シンポジウム(公募)
  • Place of Presentation: 前橋市
  • Year and Date: 2009-04-23
• [Book] 実験医学 (2011)
  • Author(s): 植木浩二郎、門脇孝
• [Book] 日本臨床 (2011)
  • Author(s): 植木浩二郎
• [Book] 糖尿病 (2011)
  • Author(s): 植木浩二郎
• [Book] 細胞 (2010)
  • Author(s): 植木浩二郎
• [Book] 実験医学 (2010)
  • Author(s): 植木浩二郎,門脇孝