Elucidation of the mechanism of iron action against anti-diabetes and search for a new therapeutic target of diabetes研究代表池田康将(IKEDA YASUMASA)

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790864
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: The University of Tokushima
• Principal Investigator: IKEDA Yasumasa 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (60432754)
• Project Period (FY): 2010 – 2011
• Keywords: 鉄 / 肥満 / 糖尿病 / 酸化ストレス

Research Abstract

It has been shown that the amount of visceral fat is related to body iron content, and body iron storage is a risk factor of the development of diabetes. We examined the effect of iron deprivation in fat tissue. Iron deprivation contributed to 1) decrease of fat weight and adipocyte size, 2) reduction of macrophage invasion in fat, 3) suppression of oxidative stress and inflammatory cytokine, 4) improvement of Akt-IRS pathway. These results suggest that iron chelation improve the development of adipocyte hypertrophy via suppression of oxidative stress, leading to the amelioration of glucose tolerance.

Research Products

• [Journal Article] Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice (2012)
  • Author(s): Tajima S*, Ikeda Y*, Sawada K, Yamano N, Horinouchi Y, Kihira Y, Ishizawa K, Izawa-Ishizawa Y, Kawazoe K, Tomita S, Minakuchi K, Tsuchiya K, Tamaki T.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 302 Pages: E77-86
  • DOI: DOI:10.1152/ajpendo.00033.2011
  • Peer Reviewed
• [Journal Article] Pathophysiological response to hypoxia-from the molecular mechanisms of malady to drug discovery : Inflammatory responses of hypoxia-inducible factor 1alpha(Hif-1alpha) in T cells observed in development of vascular remodeling (2011)
  • Author(s): Tomita S, Kihira Y, Imanishi M, Fukuhara Y, Imamura Y, Ishizawa K, Ikeda Y, Tsuchiya K, Tamaki T.
  • Journal Title: J Pharmacol Sci Volume: 115 Pages: 433-439
  • DOI: DOI:10.1254/jphs.10R22FM
  • Peer Reviewed
• [Journal Article] Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1alpha in adipocytes (2011)
  • Author(s): Kihira Y, Yamano N, Izawa-Ishizawa Y, Ishizawa K, Ikeda Y, Tsuchiya K, Tamaki T, Tomita S.
  • Journal Title: Int J Biochem Cell Biol
  • DOI: DOI:10.1016/j.biocel.2011.07.009
  • Peer Reviewed
• [Journal Article] Pharmacology in health food : Metabolism of quercetin in vivo and its protective effect against arteriosclerosis (2011)
  • Author(s): Ishizawa K, Yoshizumi M, Kawai Y, Terao J, Kihira Y, Ikeda Y, Tomita S, Minakuchi K, Tsuchiya K, Tamaki T.
  • Journal Title: J Pharmacol Sci Volume: 115 Pages: 466-470
  • DOI: DOI:10.1254/jphs.10R38FM
  • Peer Reviewed
• [Journal Article] 総説:循環器疾患と糖尿病における生体内鉄の意義 (2011)
  • Author(s): 池田康将、田島宗一郎、山野範子、土屋浩一郎、玉置俊晃
  • Journal Title: 血管 Volume: VOL.34(2) Pages: 75-85
  • URL: http://jscr21.medic.mie-u.ac.jp/system/online_det.php?no=144 & ps1=16
• [Journal Article] Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function (2011)
  • Author(s): Ikeda Y, Tajima S, Yoshida S, Yamano N, Kihira Y, Ishizawa K, Aihara K, Tomita S, Tsuchiya K, Tamaki T.
  • Journal Title: Atherosclerosis Volume: 215 Pages: 339-347
  • DOI: DOI:10.1016/j.atherosclerosis.2011.01.009
  • Peer Reviewed
• [Journal Article] Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells (2010)
  • Author(s): Tajima S, Tsuchiya K, Horinouchi Y, Ishizawa K, Ikeda Y, Kihira Y, Shono M, Kawazoe K, Tomita S, Tamaki T.
  • Journal Title: Hypertens Res Volume: 33 Pages: 713-721
  • DOI: DOI:10.1038/hr.2010.63
  • Peer Reviewed
• [Journal Article] Heparin cofactor ii protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice (2010)
  • Author(s): Sumitomo-Ueda Y, Aihara K, Ise T, Yoshida S, Ikeda Y, Uemoto R, Yagi S, Iwase T, Ishikawa K, Hirata Y, Akaike M, Sata M, Kato S, Matsumoto T.
  • Journal Title: Hypertension Volume: 56 Pages: 430-436
  • DOI: DOI:10.1161/HYPERTENSIONAHA.110.152207
  • Peer Reviewed
• [Journal Article] Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/ db mice (2010)
  • Author(s): Mihara M, Aihara K, Ikeda Y, Yoshida S, Kinouchi M, Kurahashi K, Fujinaka Y, Akaike M, Matsumoto T.
  • Journal Title: Endocrinology Volume: 151 Pages: 513-519
  • DOI: DOI:10.1210/en.2009-0661
  • Peer Reviewed
• [Journal Article] Angiotensin ii receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner (2010)
  • Author(s): Ishizawa K, Izawa-Ishizawa Y, Dorjsuren N, Miki E, Kihira Y, Ikeda Y, Hamano S, Kawazoe K, Minakuchi K, Tomita S, Tsuchiya K, Tamaki T.
  • Journal Title: Nephrol Dial Volume: 25 Pages: 364-372
  • DOI: DOI:10.1093/ndt/gfp520
  • Peer Reviewed
• [Journal Article] Matsumoto T. Androgen receptor counteracts doxorubicin-induced cardiotoxicity in male mice (2010)
  • Author(s): Ikeda Y, Aihara K, Akaike M, Sato T, Ishikawa K, Ise T, Yagi S, Iwase T, Ueda Y, Yoshida S, Azuma H, Walsh K, Tamaki T, Kato S
  • Journal Title: Mol Endocrinol Volume: 24 Pages: 1338-1348
  • DOI: DOI:10.1210/me.2009-0402
  • Peer Reviewed
• [Journal Article] Transforming growth factor-beta1 as a common Itarget molecule for development of cardiovascular diseases, renal insufficiency and metabolic syndrome (2010)
  • Author(s): Aihara K, Ikeda Y, Yagi S, Akaike M, Matsumoto T.
  • Journal Title: Cardiol Res Pract Volume: 2011 Pages: 175381
  • DOI: DOI:10.4061/2011/175381
  • Peer Reviewed
• [Presentation] Bovine Lactoferin Promotes Angiogenesis Via Akt-eNOS Dependent Pathway in Vascular Endothelial Cells (2012)
  • Author(s): Yasumasa Ikeda, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki.
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場福岡
  • Year and Date: 20120316-18
• [Presentation] Iron restriction prevents progression of diabetic nephropathy (2012)
  • Author(s): Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki.
  • Organizer: KEYSTONE SYMPOSIA 40th ANNIVERSARY 1972-2012
  • Place of Presentation: Park & Plaza Hotel, Boston, Massachusetts, USA
  • Year and Date: 20120311-16
• [Presentation] Heparin Cofactor II Promotes Angiogenesis via an AMPK-eNOS Signaling Pathway (2011)
  • Author(s): Yasumasa Ikeda, Ken-ici Aihara, Sumiko Yoshida, Yoshitaka Kihira, Keisuke Ishizawa, Yuki Izawa-Ishizawa, Shuhei Tomita, Masataka Sata, Masashi Akaike, Shigeki Kato, Toshio Matsumoto, Toshiaki Tamaki.
  • Organizer: High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions. Dolphin Hotel, Orlando
  • Place of Presentation: Florida
  • Year and Date: 20110920-24
• [Presentation] Iron elimination ameliorated glucose tolerance through suppression of oxidative stress and inflammation on fat in diabetic mice (2011)
  • Author(s): Yasumasa Ikeda, Soichiro Tajima, Noriko Yamano, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki.
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 20110803-04
• [Presentation] Estrogen action on iron metabolism. The Endocrine Society Annual Meeting 2011 (2011)
  • Author(s): Yasumasa Ikeda, Soichiro Tajima, Noriko Yamano, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki.
  • Organizer: Boston Convention & Exhibition Center
  • Place of Presentation: Boston, USA
  • Year and Date: 20110604-07
• [Presentation] 心血管リモデリングにおける男性ホルモンの作用 (2011)
  • Author(s): 池田康将、粟飯原賢一、吉田守美子、佐藤隆史、赤池雅史、玉置俊晃、加藤茂明、松本俊夫
  • Organizer: 第84回日本内分泌学会学術集会
  • Place of Presentation: シンポジウム神戸国際会議場、神戸
  • Year and Date: 20110421-23
• [Presentation] マウス下肢虚血モデルにおいて鉄キレート剤Deferoxamineは酸化ストレスとアポトーシスを抑制する (2011)
  • Author(s): 池田康将、田島壮一郎、吉田守美子、山野範子、木平孝高、石澤啓介、粟飯原賢一、冨田修平、土屋浩一郎、玉置俊晃
  • Organizer: 第40回日本心脈管作動物質学会
  • Place of Presentation: かがわ国際会議場、高松
  • Year and Date: 20110211-12
• [Presentation] Deferoxamine, an iron chelator, enhances angiogenesis through Akt-eNOS-dependent pathway in endothelial cells (2010)
  • Author(s): 池田康将、田島壮一郎、吉田守美子、山野範子、木平孝高、石澤啓介、粟飯原賢一、冨田修平、土屋浩一郎、玉置俊晃
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 梅田スカイビル大阪
  • Year and Date: 20101201-02
• [Presentation] an iron chelator, promotes angiogenesis after ischemic hind limb through Akt-eNOS-dependent pathway (2010)
  • Author(s): Yasumasa Ikeda, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki. Deferoxamine
  • Organizer: XX World Congress ISHR 2010 Kyoto International Conference Center
  • Place of Presentation: Kyoto
  • Year and Date: 20100513-16
• [Presentation] Deferoxamine, an iron chelator, promotes revascularization via endothelial cells activation
  • Author(s): 池田康将、田島壮一郎、吉田守美子、山野範子、木平孝高、石澤啓介、粟飯原賢一、冨田修平、土屋浩一郎、玉置俊晃
  • Organizer: パシフィコ横浜、第84回日本薬理学会年会
  • Place of Presentation: 横浜(震災のため開催中止)
• [Remarks] ホームページ
  • URL: http://150.59.76.31/university/servlet/index? & level=4 & reference=0/10001/3/30005/20012
• [Patent(Industrial Property Rights)] マクロファージの浸潤抑制によるインスリン抵抗性改善剤 (2011)
  • Inventor(s): 徳島大学
  • Industrial Property Rights Holder: 玉置俊晃、池田康将、土屋浩一郎
  • Industrial Property Number: 特許申請、特願2011-174001
  • Filing Date: 2011-07-25