Risk factors for diabetic nephropathy (apolipoprotein E2 allele and remnant lipoproteins) and drug intervention

• Project/Area Number: 19590155
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Ohu University
• Principal Investigator: ETO Masaaki Ohu University, 薬学部, 教授 (90133818)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 糖尿病性腎症 / レムナントリポ蛋白 / 高レムナント血症 / 高脂血症 / 腎メサンギウム細胞 / アポE2 遺伝子 / アポE2遺伝子 / TGF-β / VLDL受容体

Research Abstract

目的はわれわれの見出したアポE2遺伝子、高中性脂肪血症/高レムナント血症が糖尿病性腎症を増悪させる機序を、また薬物の効果を検討することである。アポE2遺伝型を有する糖尿病患者由来レムナントリポ蛋白が培養ヒト腎メサンギウム細胞に対してTGF-βおよび細胞外基質のmRNA を増加させることを明らかにした。さらにPPARαのリガンドであるフィブラート薬がレムナントリポ蛋白によるTGF-βおよび細胞外基質のmRNAの増加を抑制することが判明した。フィブラート薬は糖尿病患者において血中レムナントを低下させ、また腎メサンギウム細胞に直接作用して糖尿病性腎症を防御する。

Research Products

• [Journal Article] Bezafibrate suppresses the expression of TGF-β and type IV collagen in human mesangial cells loaded with remnant lipoproteins (2009)
  • Author(s): Terasawa R, Hattori Y, Agatsuma I,Saito M, Eto M
  • Journal Title: Jpn Pharmacol Ther 36 Pages: 117-122
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of ezetimibe monotherapy in hyperlipidemic patients-Ezetimibe reduces plasma remnant cholesterol- (2009)
  • Author(s): Saito M. Kumanomido A. Takigami S, Hattori Y. Agatsum I, Terasawa R, Eto M
  • Journal Title: Jpn Pharmacol Ther 36 Pages: 411-416
  • Peer Reviewed
• [Journal Article] Bezafibrate suppresses the expression of TGF-βand type IV collagen in human mesangial cells loaded with remnant lipoproteins (2009)
  • Author(s): Terasawa R, Hattori Y, Agatsuma I, Saito M, Eto M
  • Journal Title: Jpn Pharmacol Ther 37 Pages: 117-122
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of the combination therapy of pitavastatin and bezafibrate in type 2 diabetic patients with type Iib hyperlipidemia (2008)
  • Author(s): Saito M, Kumanomido A, Takigami S, Eto M
  • Journal Title: Jpn Pharmacol Ther 36 Pages: 317-323
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of ezetimibe monotherapy in hyperlipidemic patients. -Ezetimibe reduces plasma remnant cholesterol- (2008)
  • Author(s): Saito M, Kumanomido A, Takigami S, Hattori Y, Agatsuma I, Terasawa R, Eto M
  • Journal Title: Jpn Pharmacol Ther 36 Pages: 411-416
  • Peer Reviewed
• [Journal Article] A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency (2007)
  • Author(s): Okubo M, Horinishi A, Saito M, Ebara T, Endo Y, Kaku K, Murase T, Eto M
  • Journal Title: Molecular Genetics and Metabolism 92 Pages: 229-233
  • Peer Reviewed
• [Journal Article] Accelerated nephropathy in type 2 diabetic patients with type III hyperlipoproteinemia (apo E2/2 genotype), and the detrimental effects of their remnant lipoproteins on human mesangial cells (2007)
  • Author(s): Saito M, Eto M
  • Journal Title: Diabetologia (Suppl.) Pages: 31-32
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of rosuvastatin administration in type 2 diabetic patients with hypercholesterolemia (2007)
  • Author(s): Saito M, Takigami S, Tominaga M, Eto M
  • Journal Title: Jpn Pharmacol Ther 35 Pages: 1077-1083
  • Peer Reviewed
• [Journal Article] Lipids behavior and adverse effects for oral antidiabetic agents in patients with type 2 diabetes treated with sulfonylureas alone based on systematic review (2007)
  • Author(s): Mukai J, Tada H, Watanabe Y, Miura M, Katsuyama S, Shouji T. Mori K, Eto M, Suzuki T
  • Journal Title: YAKAGAKU ZASSHI 127 Pages: 1747-1756
  • NAID: 110006402960
  • Peer Reviewed
• [Journal Article] A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency (2007)
  • Author(s): Okubo M, Horinishi A, Saito M, Ebara T, Endo Y, Kaku K, Murase T, Eto M.
  • Journal Title: Molecular Genetics and Metabolism 92 Pages: 229-233
  • Peer Reviewed
• [Journal Article] Accelerated nephropathy in type 2 diabetic patients with type III hyperlipoproteinemia,and the detrimental effects of their remnant lipoproteins on human mesangial cells (2007)
  • Author(s): Saito M, Eto M
  • Journal Title: Diabetologia 50 (Suppl. Pages: 51-52
  • Peer Reviewed
• [Presentation] Bezafibrate suppresses the expression of TGF-β and type IV collagen mRNA in human mesangial cells loaded with remnant lipoproteins (2009)
  • Author(s): Eto M, Hattori Y, Terasawa R, Saito M
  • Organizer: The 45^<rd> EASD Annual Meeting (欧州糖尿病学会)
  • Place of Presentation: ウィーン
• [Presentation] 中性脂肪、なぜ、どうやって、どこまで下げるか-中性脂肪管理の重要性 (2008)
  • Author(s): 衛藤雅昭, 斉藤美恵子
  • Organizer: 第51回日本糖尿病学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-22
• [Presentation] Remnant lipoproteins and small dense LDL in patients with the metabolic syndrome (2008)
  • Author(s): Saito M, Eto M
  • Organizer: The 77^<th> EAS congress(欧州動脈硬化学会)
  • Place of Presentation: イスタンブール
• [Presentation] Accelerated nephropathy in type 2 diabetic patients with type III hyperlipoproteinemia (apo E2/2 genotype), and the detrimental effects of their remnant lipoproteins on human mesangial cells (2007)
  • Author(s): Saito M, Eto M
  • Organizer: The 43^<rd> EASD Annual Meeting (欧州糖尿病学会)
  • Place of Presentation: アムステルダム
  • Year and Date: 2007-09-18
• [Presentation] Accelerated nephropathy in type 2 diabetic patients with type III hyperlipoproteinemia,and the detrimental effects of their remnant lipoproteins on human mesangial cells (2007)
  • Author(s): Saito M, Eto M
  • Organizer: The 43rd EASD Annual Meeting(欧州糖尿病学会)
  • Place of Presentation: Amsterdam
  • Year and Date: 2007-09-18
• [Book] 「脂質異常症-基本を踏まえた実践」内科103 巻 III型高脂血症 (2009)
  • Author(s): 衛藤雅昭、服部由香、上妻いくえ、斉藤美恵子
  • Publisher: 南江堂
• [Book] 「変わる脳梗塞の再発予防~薬物療法と血圧・脂質・血糖管理」Mebio 26 巻 糖尿病治療と脳梗塞の再発予防 (2009)
  • Author(s): 衛藤雅昭、服部由香、斉藤美恵子
  • Publisher: メジカルビュー社
• [Book] 脂質異常症-III型高脂血症 (2009)
  • Author(s): 衛藤雅昭, 服部由香, 上妻いくえ, 斉藤美恵子
  • Total Pages: 5
  • Publisher: 南江堂
• [Book] 「大規模臨床試験」糖尿病における大規模臨床試験 スタチン系薬剤 (2008)
  • Author(s): 衛藤雅昭、服部由香、斉藤美恵子
  • Publisher: 日本臨床社
• [Remarks] ホームページ 奥羽大学研究紹介 衛藤雅昭
  • URL: http://www.ohu-u.ac.jp/faculty/research/researchP2.html