Obesity, atherosclerosis and RAGE-mediated inflammatory signal

• Project/Area Number: 23591329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Hyogo Medical University
• Principal Investigator: KOYAMA Hidenori 兵庫医科大学, 医学部, 准教授 (80301852)
• Co-Investigator(Kenkyū-buntansha): FUKUMOTO Shinya 大阪市立大学, 大学院医学研究科, 講師 (90381996)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Hiroshi 金沢大学, 大学院医学系研究科, 教授 (00115198)
• Research Collaborator: RAINES Elaine W. University of Washington, Department of Pathology, Professor
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 終末糖化産物受容体(RAGE) / 肥満 / メタボリックシンドローム / インスリン抵抗性 / 糖尿病 / 可溶性RAGE(ｓRAGE) / 分泌型RAGE(esRAGE) / RAGE / 可溶性RAGE / 炎症 / 血管内皮障害

Research Abstract

Receptor for advanced glycation end-products (RAGE) is deeply involved in pathogenesis of chronic diabetic vascular complications including nephropathy and atherosclerosis. In this research project, we have found that RAGE plays important roles in etiology of obesity, metabolic syndrome, and insulin resistance by using in vitro adipogenesis model system and in vivo obesity mouse model (Diabetes 2013). In clinical research, we have also found that thiazolidinediones have profound effects on RAGE system, by directly comparing with sulfonyurea in a randomized controlled trial (Atherosclerosis 2014).

Research Products

• [Journal Article] Comparison of effects of pioglitazone and glimepiride on plasma soluble RAGE and RAGE expression in peripheral mononuclear cells in type 2 diabetes : Randomized controlled trial (PioRAGE) (2014)
  • Author(s): Koyama H, Tanaka S, Monden M, Shoji T, Morioka T, Fukumoto S, Mori K, Emoto M, Shoji T, Fukui M, Fujii H, Nishizawa Y, Inaba M
  • Journal Title: Atherosclerosis Volume: 234 Pages: 329-334
  • Peer Reviewed
• [Journal Article] Comparison of effects of pioglitazone and glimepiride on plasma soluble RAGE and RAGE expression in peripheral mononuclear cells in type 2 diabetes: Randomized controlled trial (PioRAGE) (2014)
  • Author(s): Koyama H, Tanaka S, Monden M, Shoji T, Morioka T, Fukumoto S, Mori K, Emoto M, Shoji T, Fukui M, Fujii H, Nishizawa Y, Inaba M
  • Journal Title: Atherosclerosis Volume: 234 Issue: 2 Pages: 329-334
  • DOI: 10.1016/j.atherosclerosis.2014.03.025
  • Peer Reviewed
• [Journal Article] Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes. (2014)
  • Author(s): Morioka T, Emoto M, Yamazaki Y, Kawano N, Imamura S, Numaguchi R, Urata H, Motoyama K, Mori K, Fukumoto S, Koyama H, Shoji T, Inaba M
  • Journal Title: Cardiovascular Diabetology Volume: 13 Issue: 1 Pages: 10-10
  • DOI: 10.1186/1475-2840-13-10
  • Peer Reviewed
• [Journal Article] Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus. (2014)
  • Author(s): Sonoda M, Shoji T, Kimoto E, Okute Y, Shima H, Naganuma T, Motoyama K, Morioka T, Mori K, Fukumoto S, Shioi A, Koyama H, Emoto M, Inaba M
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 21 Pages: 346-354
  • NAID: 130004444725
  • Peer Reviewed
• [Journal Article] Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression. (2014)
  • Author(s): Ochi A, Mori K, Emoto M, Nakatani S, Morioka T, Motoyama K, Fukumoto S, Imanishi Y, Koyama H, Ishimura E, Inaba M
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: e88704-e88704
  • DOI: 10.1371/journal.pone.0088704
  • Peer Reviewed
• [Journal Article] Association between glycemic control and morning blood pressure surge with vascular endothelial dysfunction in type 2 diabetic patients. (2014)
  • Author(s): Yoda K, Inaba M, Hamamoto K, Yoda M, Tsuda A, Mori K, Yamada S, Emoto M, Koyama H, Imanishi Y
  • Journal Title: Diabetes Care Volume: 37 Issue: 3 Pages: 644-650
  • DOI: 10.2337/dc13-1102
  • Peer Reviewed
• [Journal Article] Receptor for advanced glycation end-products (RAGE) regulates adipocyte hypertrophy and insulin sensitivity in mice : involvement of Toll-like receptor 2 (2013)
  • Author(s): Monden M, Koyama H, Otsuka Y, Morioka T, Mori K, Shoji T, Mima Y, Motoyama K, Fukumoto S, Shioi A, Emoto M, Yamamoto H, Nishizawa Y, Kurajoh M, Yamamoto T, Inaba M
  • Journal Title: Diabetes Volume: 62 Pages: 478-489
  • Peer Reviewed
• [Journal Article] 慢性腎臓病における心血管リスクとAGE/RAGE (2013)
  • Author(s): 小山英則
  • Journal Title: 医学のあゆみ Volume: 224(8)(総説) Pages: 653-658
• [Journal Article] Increased soluble IL-2 receptor levels in serum from a patient with painless thyroiditis. (2013)
  • Author(s): Hamamoto K, Inaba M, Yamada S, Yoda M, Yoda K, Goto H, Kurajoh M, Koyama H
  • Journal Title: Thyroid Research Volume: 6 Issue: 1 Pages: 12-12
  • DOI: 10.1186/1756-6614-6-12
  • Peer Reviewed
• [Journal Article] Autonomic Function is Associated With Health-Related Quality of Life in Patients With End-Stage Renal Disease: A Case-Control Study. (2013)
  • Author(s): Fujii H, Koyama H, Fukuda S, Tokai H, Tajima S, Koizumi JI, Yamaguti K, Kuratsune H, Watanabe Y, Hirayama Y, Shoji T, Inaba M, Nishizawa Y
  • Journal Title: Journal of Renal Nutrition Volume: 23 Issue: 5 Pages: 340-347
  • DOI: 10.1053/j.jrn.2012.12.008
  • Peer Reviewed
• [Journal Article] Receptor for advanced glycation end-products (RAGE) regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2 (2013)
  • Author(s): Monden M, Koyama H, Otsuka Y, Morioka T, Mori K, Shoji T, Mima Y, Motoyama K, Fukumoto S, Shioi A, Emoto M, Yamamoto H, Nishizawa Y, Kurajoh M, Tetsuya Yamamoto T, Inaba M
  • Journal Title: Ｄｉａｂｅｔｅｓ Volume: 62 Issue: 2 Pages: 478-489
  • DOI: 10.2337/db11-1116
  • Peer Reviewed
• [Journal Article] Autonomic Function is Associated With Health-Related Quality of Life in Patients With End-Stage Renal Disease: A Case-Control Study (2013)
  • Author(s): Fujii H, Koyama H, Fukuda S, Tokai H, Tajima S, Koizumi JI, Yamaguti K, Kuratsune H, Watanabe Y, Hirayama Y, Shoji T, Inaba M, Nishizawa Y
  • Journal Title: J Ren Nutr Volume: 印刷中
  • Peer Reviewed
• [Journal Article] AGEs and cardiovascular diseases in patients with end-stage renal diseases (2012)
  • Author(s): Nishizawa Y, Koyama H, Inaba M
  • Journal Title: J Ren Nutr Volume: 22(1)(総説) Pages: 128-33
  • Peer Reviewed
• [Journal Article] AGE/RAGEとメタボリックシンドローム (2012)
  • Author(s): 小山英則
  • Journal Title: 兵医大医会誌 Volume: 37(1)(総説) Pages: 89-94
• [Journal Article] Decreased serum adrenal androgen dehydroepiandrosterone sulfate and mortality in hemodialysis patients. (2012)
  • Author(s): Kakiya R, Shoji T, Ishimura E, etl.
  • Journal Title: Nephrol Dial Transplant Volume: 27 Issue: 10 Pages: 3915-3922
  • DOI: 10.1093/ndt/gfs162
  • Peer Reviewed
• [Journal Article] Antialbuminuric advantage of cilnidipine compared with L-type calcium channel blockers in type 2 diabetic patients with normoalbuminuria and microalbuminuria (2012)
  • Author(s): Fukumoto S, Ishimura E, Motoyama K, Morioka T, Kimoto E, Wakikawa K, Shoji S, Koyama H, Shoji T, Emoto M, Nishizawa Y, Inaba M
  • Journal Title: Diabetes Res Clin Pract Volume: 97 Pages: 91-98
  • Peer Reviewed
• [Journal Article] Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres (2012)
  • Author(s): Mima Y, Fukumoto S, Koyama H, Okada M, Tanaka S, Shoji T, Emoto M, Furuzono T, Nishizawa Y, Inaba M
  • Journal Title: PLoS One Volume: 7 Issue: 4 Pages: e35199-e35199
  • DOI: 10.1371/journal.pone.0035199
  • Peer Reviewed
• [Journal Article] Relationship between serum allantoin and urate in healthy subjects and effects of benzbromarone in gout patients (2012)
  • Author(s): Kurajoh M, Koyama H, Shoji T, Sumida C, Yamamoto A, Tsutsumi Z, Moriwaki Y, Yamamoto T, Koga M
  • Journal Title: Int J Clin Pharmacol Ther Volume: 50 Pages: 265-71
  • Peer Reviewed
• [Journal Article] Association of endothelial and vascular smooth muscle dysfunction with cardiovascular risk factors, vascular complications, and subclinical carotid atherosclerosis in type 2 diabetic patients. (2012)
  • Author(s): Kawano N, Emoto M, Mori K, Yamazaki Y, Urata H, Tsuchikura S, Motoyama K, Morioka T, Fukumoto S, Shoji T, Koyama H, Okuno Y, Nishizawa Y, Inaba M
  • Journal Title: J Atheroscler Thromb Volume: 19(3) Pages: 276-84
  • NAID: 130004444588
  • Peer Reviewed
• [Journal Article] AGEs and cardiovascular diseases in patients with end-stage renal diseases. (2012)
  • Author(s): Nishizawa Y, Koyama H, Inaba M
  • Journal Title: J Ren Nutr Volume: 22(1) Pages: 128-33
  • Peer Reviewed
• [Journal Article] Comparison of the effect of cilostazol with aspirin on circulating endothelial progenitor cells and small-dense LDL cholesterol in diabetic patients with cerebral ischemia: a randomized controlled pilot trial. (2011)
  • Author(s): Ueno H, Koyama H, Mima Y, Fukumoto S, Tanaka S, Shoji T, Emoto M, Shoji T, Nishizawa Y, Inaba M
  • Journal Title: J Atheroscler Thromb Volume: 18(10): Pages: 883-90
  • NAID: 130004444479
  • Peer Reviewed
• [Journal Article] Active vitamin D and acute respiratory infections in dialysis patients. (2011)
  • Author(s): Tsujimoto Y, Tahara H, Shoji T, Emoto M, Koyama H, Ishimura E, Tabata T, Nishizawa Y, Inaba M
  • Journal Title: Clin J Am Soc Nephrol Volume: 6(6): Pages: 1361-7
  • Peer Reviewed
• [Journal Article] Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease. (2011)
  • Author(s): Ueno H, Koyama H, Fukumoto S, Tanaka S, Shoji T, Shoji T, Emoto M, Tahara H, Inaba M, Kakiya R, Tabata T, Miyata T, Nishizawa Y
  • Journal Title: Metabolism Volume: 60(4) Pages: 453-9
  • Peer Reviewed
• [Journal Article] Biochemistry of uridine in plasma. (2011)
  • Author(s): Yamamoto T, Koyama H, Kurajoh M, Shoji T, Tsutsumi Z, Moriwaki Y
  • Journal Title: Clin Chim Acta Volume: 412(19-20): Pages: 1712-24
  • Peer Reviewed
• [Journal Article] 21-hydroxylase deficiency associated with male infertility: report of 2 cases with gene analyses. (2011)
  • Author(s): Sumida C, Kondoh N, Kurajoh M, Koyama H, Tsutsumi Z, Moriwaki Y, Yamamoto T
  • Journal Title: Intern Med Volume: 50(12) Pages: 1317-21
  • NAID: 130000770499
  • Peer Reviewed
• [Journal Article] Effects of bovine milk ingestion on urinary excretion of oxypurinol and uric acid. (2011)
  • Author(s): Kurajoh M, Ka T, Okuda C, Yamamoto A, Tsutsumi Z, Koyama H, Moriwaki Y, Yamamoto T
  • Journal Title: Int J Clin Pharmacol Ther Volume: 49(6) Pages: 366-70
  • Peer Reviewed
• [Presentation] RAGEおよび可溶性RAGEに対するピオグリタゾンとグリメピリドの無作為群間比較試験(PioRAGE) (2013)
  • Author(s): 小山英則、田中新二、門田真砂世、三間洋平、庄司拓仁、福本真也、絵本正憲、森岡与明、森克仁、庄司哲雄、福井充、藤井比佐子、山本徹也、西沢良記、稲葉雅章
  • Organizer: 第56回日本糖尿病学会
  • Place of Presentation: 熊本
  • Year and Date: 2013-05-17
• [Presentation] ヒト血管内皮細胞においてTumor necrosis factor-αはJNK-, p38 MAP kinaseとATF4を介して終末糖化産物受容体(RAGE)のsheddingを促進する (2013)
  • Author(s): 小山英則、門田真砂世、庄司拓仁、森岡与明、蔵城雅文、塩井淳、山本徹也、稲葉雅章
  • Organizer: 第86回日本内分泌学会
  • Place of Presentation: 仙台
  • Year and Date: 2013-04-26
• [Presentation] Brain-Derived Neurotrophic Factor と動脈硬化、心拍変動の関連． (2013)
  • Author(s): 角谷 学、神埼暁慶、蔵城雅文、庄司拓仁、白石順、角田千尋、森脇優司、山本徹也、小山英則
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 東京
• [Presentation] Interaction among heart rate variability, obstructive sleep apnea, arterial thickness and arterial stiffness in patients with cardiovascular risks. (2013)
  • Author(s): Kadoya M, Kurajoh M, Shoji T, Kanzaki A, Shiraishi J, Sumida C, Moriwaki Y, Yamamoto T, Koyama H
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 東京
• [Presentation] 2型糖尿病患者におけるピオグリタゾンとグリメピリドのRAGEおよび可溶性RAGEに対する影響：無作為群間比較試験、PioRAGE． (2013)
  • Author(s): 小山英則、田中新二、門田真砂世、三間洋平、庄司拓仁、福本真也、絵本正憲、森岡与明、森 克仁、庄司哲雄、山本徹也、西沢良記、稲葉雅章
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 東京
• [Presentation] 疲労、睡眠の質、自律神経機能と血中brain-derived neurotrophic factorの相互関係． (2013)
  • Author(s): 神崎暁慶、角谷 学、蔵城雅文、庄司拓仁、白石 順、角田千尋、森脇優司、山本徹也、福田早苗、渡辺恭良、小山英則
  • Organizer: 第9回日本疲労学会
  • Place of Presentation: 秋田
• [Presentation] 2型糖尿病患者における間接熱量測定の検討：心血管疾患既往および頸動脈硬化との関連． (2013)
  • Author(s): 庄司拓仁、小山英則、蔵城雅文、神崎暁慶、白石 順、角谷 学、角田千尋、森脇優司、山本徹也
  • Organizer: 第56回日本糖尿病学会
  • Place of Presentation: 熊本
• [Presentation] RAGEおよび可溶性RAGEに対するピオグリタゾンとグリメピリドの無作為群間比較試験(PioRAGE)． (2013)
  • Author(s): 小山英則、田中新二、門田真砂世、三間洋平、庄司拓仁、福本真也、絵本正憲、森岡与明、森 克仁、庄司哲雄、福井 充、藤井比佐子、山本徹也、西沢良記、稲葉雅章
  • Organizer: 第56回日本糖尿病学会
  • Place of Presentation: 熊本
• [Presentation] ヒト血管内皮細胞においてTumor necrosis factor-αはJNK-, p38 MAP kinaseとATF4を介して終末糖化産物受容体(RAGE)のsheddingを促進する． (2013)
  • Author(s): 小山英則、門田真砂世、庄司拓仁、森岡与明、蔵城雅文、塩井 淳、山本徹也、稲葉雅章
  • Organizer: 第86回日本内分泌学会
  • Place of Presentation: 仙台
• [Presentation] 痛風患者におけるHMGB1の検討 (2013)
  • Author(s): 堤 善多、小山英則，庄司拓仁，藏城雅文，角田千尋、角谷 学、森脇優司，山本徹也
  • Organizer: 第46回日本痛風・核酸代謝学会
  • Place of Presentation: 東京
• [Presentation] ヒト血管内皮細胞においてTumor necrosis factor-はJNK-, p38 MAP kinaseとATF4を介して終末糖化産物受容体(RAGE)のsheddingを促進する (2013)
  • Author(s): 小山英則、門田真砂世、庄司拓仁、森岡与明、蔵城雅文、塩井 淳、山本徹也、稲葉雅章
  • Organizer: 第86回日本内分泌学会
  • Place of Presentation: 仙台
• [Presentation] 尿酸・アラントイン値・酸化ストレスマーカーとの関連からみた尿酸の酸化・抗酸化作用の意義 (2013)
  • Author(s): 藏城雅文，小山英則，白石 順，角田千尋、庄司拓仁，山本麻子、堤 善多、森脇優司，山本徹也、古賀正史
  • Organizer: 第46回日本痛風・核酸代謝学会
  • Place of Presentation: 東京
• [Presentation] RAGEおよび可溶性RAGEに対するピオグリタゾンとグリメピリドの無作為群間比較試験（PioRAGE） (2013)
  • Author(s): 小山英則、田中新二、門田真砂世、三間洋平、庄司拓仁、福本真也、絵本正憲、 森岡与明、 森 克仁、 庄司哲雄、福井 充、 藤井比佐子、山本徹也、西沢良記、稲葉雅章
  • Organizer: 第56回日本糖尿病学会
  • Place of Presentation: 熊本
• [Presentation] 糖尿病足病変―血流障害のトピックス (2011)
  • Author(s): 小山英則
  • Organizer: 第26回日本糖尿病合併症学会シンポジウム4糖尿病足のケア
  • Place of Presentation: 大宮
  • Year and Date: 2011-10-14
• [Presentation] AGEs/RAGE系から動脈硬化・メタボリックシンドロームを考える (2011)
  • Author(s): 小山英則
  • Organizer: 第11回日本抗加齢医学会シンポジウム24:老化危険因子としてのAGEsおよびRAGE
  • Place of Presentation: 京都
  • Year and Date: 2011-05-29
• [Presentation] メタボリックシンドロームと炎症・動脈硬化一receptor for advanced glycation end-products(RAGE)を介したクロストーク (2011)
  • Author(s): 小山英則、門田真砂世、福本真也、蔵城雅文、山本徹也、稲葉雅章
  • Organizer: 第84回日本内分泌学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-23
• [Presentation] AGEs/RAGE系から動脈硬化・メタボリックシンドロームを考える (2011)
  • Author(s): 小山英則
  • Organizer: 第11回日本抗加齢医学会 シンポジウム24：老化危険因子としてのAGEsおよびRAGE(招待講演)
  • Place of Presentation: 京都
• [Presentation] 糖尿病足病変―血流障害のトピックス (2011)
  • Author(s): 小山英則
  • Organizer: 第26回日本糖尿病合併症学会 シンポジウム4 糖尿病足のケア(招待講演)
  • Place of Presentation: 大宮
• [Presentation] Tumor necrosis factor- stimulates shedding of receptor for advanced glycation end-products through JNK-, p38-MAP kinase and ATF4 pathway in human endothelial cells (2011)
  • Author(s): Monden M, Koyama H, Morioka T, Mori K, Shoji T, Fukumoto S, Tanaka S, Kurajyo M, Yamamoto T, Shioi A, Nishizawa Y, Inaba M
  • Organizer: 第43回日本動脈硬化学会
  • Place of Presentation: 札幌
• [Presentation] Decreased platelet activation is a predictor for cardiovascular diseases in end-stage renal disease patients with anemia or inflammation. (2011)
  • Author(s): Kurajyo M, Koyama H, Ueno H, Shoji T, Fukumoto S, Tanaka S, Shoji T, Emoto M, Tsujimoto Y, Tabata T, Yamamoto T, Nishizawa Y, Inaba M:
  • Organizer: 第43回日本動脈硬化学会
  • Place of Presentation: 札幌
• [Presentation] Decrease of circulating endothelial progenitor cells is a strong predictor for cardiovascular diseases in end-stage renal disease patients. (2011)
  • Author(s): Koyama H, Ueno H, Shoji T, Fukumoto S, Tanaka S, Shoji T, Emoto M, Tsujimoto Y, Tabata T, Kurajyo M, Yamamoto T, Nishizawa Y, Inaba M
  • Organizer: 第43回日本動脈硬化学会
  • Place of Presentation: 札幌
• [Book] 3.各種バイオマーカーの循環器疾患における意義.V. AGE (advanced glycation end products)/soluble RAGE (receptor for AGE).循環器病のバイオマーカー (2012)
  • Author(s): 小山英則(井上晃男編)
  • Publisher: メディカルビュー社、東京
• [Book] Cardiovascular complications in renal failure: implications of advanced glycation end-products and their receptor, RAGE. In: Oxidative Stress in Applied Basic Research and Clinical Practice ‘Renal Disorders’ (2011)
  • Author(s): Koyama H, Nishizawa Y (ed. Miyata T. Eckardt KU, Nangaku M)
  • Publisher: The Humana Press / Springer Science
• [Book] AGE/RAGE as a Mediator of Insulin Resistance or Metabolic Syndrome: Another Aspect of Metabolic Memory? In: Biomedical Science, Engineering and Technology (2011)
  • Author(s): Koyama H and Yamamoto T (ed. Ghista DN)
  • Publisher: InTech