Dysfunction of apolipoprotein A-I reabsorption in diabetic proximal tubule

• Project/Area Number: 25860414
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kitasato University
• Principal Investigator: KUROSAKI Yoshifumi 北里大学, 医療衛生学部, 助教 (20602030)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 糖尿病性腎症 / キュビリン / Apo A-I / apoA-I / Cubilin / インスリン抵抗性

Outline of Final Research Achievements

Effects of　nonenzymatic glycation on apo A-I reabsorption via cubilin in proximal tubule were evaluated. It was clarified by using cubilin peptide-coated ELISA that glycation impaired the binding properties of apo A-I to cubilin. Additionally the binding capacity and the uptake of glycated apo A-I to human proximal tubular cell diminished. Our results suggested that nonenzymatic glycation diminished the binding capacity of apo A-I to cubilin, may result in the decrease of apo A-I reabsorption by proximal tubule. In the type 2 diabetes model rat with normoalbuminuria (by feeding high fat-diet wihtin 4 weeks), apo A-I were not detected in urine.

Research Products

• [Journal Article] Semiquantitative Analysis of Apolipoprotein A-I Modified by Advanced Glycation End Products in Diabetes Mellitus. (2013)
  • Author(s): Kurosaki Y, Tsukushi T, Munekata S, Akahoshi T, Moriya T, Ogawa Z.
  • Journal Title: J Clin Lab Anal Volume: Epub ahead of print Issue: 3 Pages: 231-236
  • DOI: 10.1002/jcla.21591
  • Peer Reviewed
• [Presentation] 尿アルブミン正常糖尿病ラットにおけるアンジオテンシンⅡ依存酸化ストレスが腎メガリン発現に及ぼす影響 (2014)
  • Author(s): 黒崎祥史、山田優也、井本明美、土筆智晶、小幡進、十良澤勝雄、鈴木英明、市川毅、横場正典、池永秀樹、青木芳和、市川尊文、竹中恒夫、片桐真人、石井直仁
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡国際会議場 （福岡県福岡市）
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] The contribution of angiotensin II-dependent oxidative stress to megalin expression in the renal cortex during the normoalbuminuric stage of diabetes mellitus in the rat. (2014)
  • Author(s): Yoshifumi Kurosaki, Yuya Yamada, Pamela K. Carmines, Tomoaki Tsukushi, Akemi Imoto, Tsuyoshi Ichikawa, Masanori Yokoba, Susumu Obata, Hideki Ikenaga, Yoshikazu Aoki, Tsuneo Takenaka, Takafumi Ichikawa, Masato Katagiri, Naohito Ishii.
  • Organizer: AACC 2014 Annual Meeting and Clinical Lab Exposition
  • Place of Presentation: McCormick Place (USA, Chicago)
  • Year and Date: 2014-07-27 – 2014-07-31
• [Presentation] Angiotensin II-dependent oxidative stress and increased hypoxia-inducible factor-1α expression in the renal cortex during the normoalbuminuric stage of diabetic mellitus in the rat. (2014)
  • Author(s): Y. Yamada, Y. Kurosaki, P. K. Carmines, T. Tsukushi, A. Imoto, T. Ichikawa, M. Yokoba, H. Ikenaga, Y. Aoki, T. Takenaka, T. Ichikawa, M. Katagiri, N. Ishii
  • Organizer: AACC 2014 Annual Meeting and Clinical Lab Exposition
  • Place of Presentation: McCormick Place (USA, Chicago)
  • Year and Date: 2014-07-27 – 2014-07-31
• [Presentation] Impact of angiotensin II receptor blockade on the renal cortical tissue renin-angiotensin system during the normoalbuminuric stage of diabetic mellitus in the rat. (2014)
  • Author(s): N. Ishii, Y. Kurosaki, P. K. Carmines, Y. Yamada, T. Tsukushi, A. Imoto, T. Ichikawa, M. Yokoba, H. Suzuki, H.Ikenaga, Y. Aoki, T. Takenaka, T. Ichikawa, M. Katagiri
  • Organizer: AACC 2014 Annual Meeting and Clinical Lab Exposition
  • Place of Presentation: McCormick Place (USA, Chicago)
  • Year and Date: 2014-07-27 – 2014-07-31
• [Presentation] 腎症前期糖尿病ラットの腎皮質における酸化ストレス抑制と組織レニン・アンジオテンシン系の関連について (2013)
  • Author(s): 石井直仁、黒崎祥史、山田優也、横場正典、市川毅、土筆智晶、池永秀樹、青木芳和、市川尊文、竹中恒夫、片桐真人
  • Organizer: 第53回日本臨床化学会年次学術集会
  • Place of Presentation: あわぎんホール（徳島県徳島市）
• [Presentation] Angiotenin-converting enzyme inhibition curbs tyrosine nitration of mitochondrial proteins in the renal cortex during the early stage of diabetes mellitus in rats. (2013)
  • Author(s): Naohito Ishii, Pamela K. Carmines, Masanori Yokoba, Hideki Ikenaga, Tsuyoshi Ichikawa, Yuya Yamada, Yoshifumi Kurosaki, Tomoaki Tsukushi, Yoshio Kodera, Masamichi Oh-Ishi, Yoshikazu Aoki, Tadakazu Maeda, Takafumi Ichikawa, Tsuneo Takenaka, Masato Katagiri.
  • Organizer: Human Proteome Organization 12th Annual World Congress
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 腎症前期糖尿病ラットの腎皮質におけるHypoxia inducible factor α 発現について (2013)
  • Author(s): 黒崎祥史、山田優也、土筆智晶、横場正典、市川毅、宇治橋善勝、池永秀樹、青木芳和、市川尊文、竹中恒夫、片桐真人、石井直仁
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
• [Presentation] 健常者における経鼻的持続気道陽圧呼吸による横隔膜の動きの変化に対する体位の影響について (2013)
  • Author(s): 山田優也、横場正典、黒崎祥史、市川毅、土筆智晶、宇治橋善勝、市川尊文、石井直仁、片桐真人
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
• [Presentation] Expiratory muscle and upper airway muscle activity during reverse sniff. (2013)
  • Author(s): Tsuyoshi Ichikawa, Masanori Yokoba, Akira Takakura, Masahiko Kimura, Naohito Ishii, Michiko Kimura, Mikiko Ishihara, Yoshifumi Kurosaki, Yuya Yamada, Yuko Mitsui, Atsuhiko Matsunaga, Noriyuki Masuda, Masato Katagiri.
  • Organizer: The 18 th Congress of Asia-Pacific Society of Respirology
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）