Investigations of S1P receptors as novel therapeutic targets for metabolic syndrome

• Project/Area Number: 20591057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nagoya University
• Principal Investigator: HAMADA Yoji Nagoya University, 医学系研究科, 寄附講座准教授 (20293706)
• Co-Investigator(Kenkyū-buntansha): NAGASAKI HIROSHI 名古屋大学, 大学院・医学系研究科, 寄附講座講師 (30420384)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: メタボリック・シンドローム / 脂肪細胞 / S1P受容体 / アディポサイトカイン

Research Abstract

Increased secretion of inflammatory adipocytekines has been related to the pathogenesis of metabolic syndrome. Present study revealed that sphingosine 1-phosphate (S1P) stimulated inflammatory adipocytokine secretion such as IL-6 and MCP-1 from mature adipocytes, mediated by an receptor S1P3 among five subtype receptors for S1P. The specific inhibitor for S1P3 was effective to suppress these inflammatory adipocytokines, which suggest that the S1P3 specific inhibitor may ameliorate the pathophysiology of metabolic syndrome.

Research Products

• [Journal Article] Palmitate induces apoptosis in Schwann cells via both ceramide-dependent and independent pathways. (2011)
  • Author(s): Suzuki J, Akahane K, Nakamura J, Naruse K, Kamiya H, Himeno T, Nakamura N, Shibata T, Kondo M, Nagasaki H, Fujiya A, Oiso Y, Hamada Y.
  • Journal Title: Neuroscience 176 Pages: 188-198
  • Peer Reviewed
• [Journal Article] Palmitate induces apoptosis in Schwann cells via both ceramide-dependentand independent pathways (2011)
  • Author(s): 鈴木淳也
  • Journal Title: Neuroscience Volume: 176 Pages: 188-198
  • Peer Reviewed
• [Journal Article] Low-serum culture system improves the adipogenic ability of visceral adipose tissue-derived stromal cells (2011)
  • Author(s): 長崎弘
  • Journal Title: Cell Biology International Volume: 印刷中(未定)
  • Peer Reviewed
• [Journal Article] High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt (2011)
  • Author(s): 中村信久
  • Journal Title: Journal of Diabetes Investigation Volume: 印刷中(未定)
  • Peer Reviewed
• [Journal Article] Adiponectin promotes migration activities of endothelial progenitor cells via Cdc42/Rac1. (2009)
  • Author(s): Nakamura N, Naruse K, Matsuki T, Hamada Y, Nakashima E, Kamiya H, Matsubara T, Enomoto A, Takahashi M, Oiso Y, Nakamura J
  • Journal Title: FEBS Lett 583 Pages: 2457-2463
  • Peer Reviewed
• [Journal Article] Polymorphism in resistin promoter region at -420 determines the serum resistin levels and may be a risk marker of stroke in Japanese type 2 diabetic patients. (2009)
  • Author(s): Tsukahara T, Nakashima E, Watarai A, Hamada Y, Naruse K, Kamiya H, Nakamura N, Kato N, Hamajima N, Sekido Y, Niwa T, Tomita M, Oiso Y, Nakamura J
  • Journal Title: Diabetes Res Clin Pract 84 Pages: 179-186
  • Peer Reviewed
• [Journal Article] Adiponectin promotes migration activities of endothelial progenitor cellsvia Cdc42/Rac1 (2009)
  • Author(s): Nakamura N, Naruse K, Matsuki T, et al.
  • Journal Title: FEBS Lett 583 Pages: 2457-2463
  • Peer Reviewed
• [Journal Article] Polymorphism in resistin promoter region at -420 determines the serum resistin levels and may be a risk marker of stroke in Japanese type 2 diabetic patients (2009)
  • Author(s): Tsukahara T, Nakashima E, Watarai A, et al.
  • Journal Title: Diabetes Res Clin Pract 84 Pages: 179-86
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 濱田洋司(分担執筆)
  • Journal Title: 広範囲 血液・尿化学検査 免疫学的検査(1)(日本臨床) Pages: 446-500
• [Journal Article] Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats (2008)
  • Author(s): Shibata T, Naruse K, Kamiya H, Kozakae M, Kondo M, Yasuda Y, Nakamura N, Ota K, Tosaki T, Matsuki T, Nakashima E, Hamada Y, Oiso Y, Nakamura J
  • Journal Title: Diabetes 57 Pages: 3099-3107
  • Peer Reviewed
• [Journal Article] High glucose-induced upregulation of Rho/Rho-kinase via platelet-derived growth factor receptor-beta increases migration of aortic smooth muscle cells. (2008)
  • Author(s): Akiyama N, Naruse K, Kobayashi Y, Nakamura N, Hamada Y, Nakashima E, Matsubara T, Oiso Y, Nakamura J
  • Journal Title: J Mol Cell Cardiol 46 Pages: 326-332
  • Peer Reviewed
• [Journal Article] Reduced NGF secretion by Schwann cells under the high glucose condition decreases neurite outgrowth of DRG neurons. (2008)
  • Author(s): Tosaki T, Kamiya H, Yasuda Y, Naruse K, Kato K, Kozakae M, Nakamura N, Shibata T, Hamada Y, Nakashima E, Oiso Y, Nakamura J
  • Journal Title: Exp Neurol 213 Pages: 381-387
  • Peer Reviewed
• [Journal Article] Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha 2 (GPA2) and beta 5 (GPB5). (2008)
  • Author(s): Okajima Y, Nagasaki H, Suzuki C, Suga H, Ozaki N, Arima H, Hamada Y, Civelli O, Oiso Y
  • Journal Title: Regul Pept 148 Pages: 62-67
  • Peer Reviewed
• [Journal Article] High glucose-induced upregulation of Rho/Rho kinase vai platelet-derived growth factor receptor-βincreases migration of aortic smooth muscle cells. (2008)
  • Author(s): Akiyama N, Narase K, Kobayashi Y, et al.
  • Journal Title: J Mol Cell Cardiol 45 Pages: 326-332
  • Peer Reviewed
• [Journal Article] The melanin-concentrating hormone system and its physiological functions. (2008)
  • Author(s): Saito Y, Nagasaki H.
  • Journal Title: Results Probl Cell Differ 46 Pages: 159-79
  • Peer Reviewed
• [Journal Article] Anti-gly cation effect of gliclazide on in-vitro AGE formation from glucose and methylglyoxal (2008)
  • Author(s): Li W, Ota K, Nakamura J, et al.
  • Journal Title: Exp Biol Med 233 Pages: 176-179
  • Peer Reviewed
• [Journal Article] Biochemical roles of the olgosaccharide chains in thyrostimulin, a hetero dimeric hormone of glycoprotein hormone subunits alpha2 (GPA2) and beta5(GPB5) (2008)
  • Author(s): Okajima Y, Nagasaki H, Suzuki C, et al.
  • Journal Title: Regulatory Peptides 148 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Low serum culture system improves adipogenic ability of visceral adipose tissue derived stromal cell.
  • Author(s): Nagasaki H, Suzuki T, Hashimoto H, Shang QL, Yoshimura T, Kondo T, Ozaki T, Maruyama S, Johmori T, Oiso Y, Hamada Y.
  • Journal Title: Cell Biology International In press
  • Peer Reviewed
• [Presentation] 胆汁酸代謝とインスリン抵抗性に対するα-グルコシダーゼ阻害薬ミグリトールの作用 (2010)
  • Author(s): 濱田洋司、長崎弘、渕上昌弘、大磯ユタカ
  • Organizer: 第31回日本肥満学会年次学術集会
  • Place of Presentation: 前橋市
  • Year and Date: 2010-10-22
• [Presentation] メタボリックシンドロームにおける血清遊離脂肪酸およびセラミド濃度の検討-病態および脂質摂取との関連について (2010)
  • Author(s): 濱田洋司、河村孝彦、長崎弘、鈴木淳也、大磯ユタカ
  • 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] パルミチン酸によるSchwann細胞のアポトーシス誘導機序の検討 (2009)
  • Author(s): 鈴木淳也、太田貴美子、神谷英紀、中村二郎、長崎弘、大磯ユタカ、濱田洋司
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-22
• [Presentation] The functions of bone marrow-derived mononuclear cells and their therapeutic efficacy on diabetic polyneuropathy are affected by their age (2009)
  • Author(s): Kondo, M ; Kamiya, H ; Shibata, T, et al
  • Organizer: 45 th Annual Meeting of European Association for the Study of Diabetes(EASD)
  • Place of Presentation: Vienna, Austria
• [Presentation] グリメピリドがヒト大網由来幹細胞のアディポサイトカイン発現に及ぼす影響 (2009)
  • Author(s): 吉村智子、長崎弘、野田幸弘, 他
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] 2型糖尿病において末梢血単核球のアルドース還元酵素遺伝子発現量は頸動脈病変と相関する (2009)
  • Author(s): 成瀬桂子、小林泰子、中村信久, 他
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] レジスチンによる単球接着能の亢進とそのメカニズムに関する研究 (2009)
  • Author(s): 松木孝、中村信久、中島英太郎, 他
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] 糖尿病性末梢神経障害に対する骨髄単核球移植治療の効果 (2009)
  • Author(s): 近藤正樹、神谷英紀、柴田大河, 他
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] 3T3-L1脂肪細胞からのInterleukin-6分泌に対するセラミド代謝の影響 (2008)
  • Author(s): 濱田洋司、長崎弘、鈴木淳也、大磯ユタカ
  • Organizer: 第51回日本糖尿病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] ヒト大網脂肪由来幹細胞における肥満関連遺伝子発現の検討 (2008)
  • Author(s): 長崎弘, 近藤貴昭, 鈴木猛志, 他
  • Organizer: 第51回日本糖尿病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] Circulating Endothelial Progenitor Cells Are Associated with Vascular Disorder in Healthy and Type 2 Diabetic Subjects (2008)
  • Author(s): K Naruse, Y Kobayashi, N Nakamura
  • Organizer: The 68th the American Diabetes Association Scientific Sessions
  • Place of Presentation: San Francisco, U. S. A
• [Presentation] A TSH-like heterodimer thyrostimulin is localized in the corticotroph and ACTH producing tumor (2008)
  • Author(s): Nagasaki H, Okajima, Y, Suga, H
  • Organizer: The 89^<th> annual meeting, The Endocrine Society
  • Place of Presentation: San Francisco, U.S.A.
• [Book] 新時代の糖尿病学(4)(分担執筆) (2008)
  • Author(s): 濱田洋司
  • Total Pages: 712
  • Publisher: 日本臨床
• [Book] 新時代の糖尿病学(4) (2008)
  • Author(s): 濱田洋司(分担執筆)
  • Publisher: 日本臨床