Role of adiponectin and its binding to the glomeruli in development and progression of diabetic nephropathy

• Project/Area Number: 16590800
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Teikyo University
• Principal Investigator: UCHIDA Shunya Teikyo University, 医学部, 教授 (50151882)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Diabetic nephropathy / Nephrin / α3-integrin / α-dystroglycan / Adiponectin / Endothelial cell / Mesangial cell / Double immunostaining / 受容体 / 糸球体毛細血管内皮細胞 / メサンジウム細胞 / RT-PCR / ストレプトゾトシンラット / アディポネクチン受容体 / 免疫組織化学

Research Abstract

Since a sizable number of diabetic patients enter regular dialysis, elucidation of the mechanism whereby diabetic nephropathy progresses is of immediate importance Adiponectin (ADPN), a 30 kDa protein exclusively secreted by adipocytes, acts as an anti-diabetic and anti-atherogenic hormone It has recently been reported that plasma concentration of ADPN is reduced in diabetes in both humans and experimental animals. However, the pathophysiological significance of ADPN is largely unknown. Thus, we have investigated a role of ADPN in the pathogenesis of diabetic nephropathy. Mild diabetes was induced in 7 week-old rats by a single i. v. injection of streptozotocin (40 mg/kg). The rats remained non-ketotic without insulin throughout the experimental period of 24 weeks. Vehicle-injected rats were used as control. At 8, 16 and 24 weeks after the injection of streptozotocin, blood and urine samples were collected, and rats were sacrificed. In diabetic rats, fasting blood glucose, total choles terol and triglyceride increased several folds from the values in control rats during 4 to 24 weeks. HbAlc also increased from <2.5% to 8.2%. Beyond 12 weeks, urinary protein excretion increased modestly in diabetic rats from 15 to 45 mg/day. Neither blood pressure nor plasma creatinine changed significantly. ADPN immunostaining in the glomerulus was faint in the control rats, whereas the immunostaining intensified in the diabetic rat with time. Confocal laser scanning mioroscopy revealed that ADPN immunolabeling was confined to endothelial cells and, to a lesser extent, mesangial cells as evidenced by double immunostaining with anti-PECAM (a marker of endothelial cells) or with anti-Thy-1 (a marker ofmesangial cells). Plasma ADPN levels in diabetic rats were reduced to half of those in control rats. These results show that ADPN binds to glomerular endothelial cells and, to a lesser extent, mesangial cells, and this cell-selective binding increases in diabetes, suggesting that ADPN may protect the structure and function of the glomerular capillary in diabetic nephropathy.

Research Products

• [Journal Article] Reliability of rapid urinary test for anitibody to Helicobactor pylori in adult patients with proteinuria. (2006)
  • Author(s): Yamamoto, T, et al.
  • Journal Title: Diagnostic Microbiology and Infectious Disease 54・2 Pages: 105-108
• [Journal Article] ストレプトゾトシン糖尿病ラットにおけるpodocyte関連蛋白発現の経時的変化について. (2005)
  • Author(s): 神田佳子
  • Journal Title: 帝京医学雑誌 28 Pages: 69-77
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 「研究成果報告書概要(欧文)」より (2005)
  • Author(s): Y Kanda
  • Journal Title: Teikyo Medical Journal 28 (2) Pages: 69-77
• [Journal Article] Autoantibodies against carbonic anhydrase II are increased in renal tubular acidosis associated with Sjogren syndrome. (2005)
  • Author(s): Takemoto, F, et al.
  • Journal Title: Amerlcan Journal of Medicine 118・2 Pages: 181-184
• [Journal Article] Effect of vitamin E-bonded dialyzer on eosinophilia in haemodialysis patients. (2005)
  • Author(s): Kojima K, et al.
  • Journal Title: Nephrology Dialysis and Transplantation 20・9 Pages: 1932-1935
• [Journal Article] Autoantibodies against carbonic anhydrase II are increased in renal tubular acidosis associated with Sjogren syndrome. (2005)
  • Author(s): Takemoto F, Uchida S, et al.
  • Journal Title: American Journal of Medicine 118・2 Pages: 181-184
• [Journal Article] Podocyte flattening and disorder of glomerular basement membrane are associated with splitting of dystroglycan-matrix interaction. (2004)
  • Author(s): Kojima K, Uchida S, et al.
  • Journal Title: Journal of American Society of Nephrology 15・8 Pages: 2079-2089
• [Presentation] ストレプトゾトシン(STZ)誘発糖尿病ラットにおけるpodocyte関連蛋白の発現変化. (2004)
  • Author(s): 神田佳子, 松本なつき, 冨丘 聡, 高橋和志, 秋元寛正, 角田祥子, 名越 洋, 新井隆己, 松井克之, 中村一路, 河内 裕, 清水不二雄, 内田俊也.
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] ストレプトゾトシン誘発糖尿病ラットにおけるadiponectin受容体の腎内局在. (2004)
  • Author(s): 竹本文美, 孫 大輔, 中西昌平, 星野純一, 澤直樹, 田上哲夫, 横田雅史, 香取秀幸, 乳原善文, 高市憲明, 原茂子, 神田佳子, 内田俊也, 中野泰子, 門脇 孝
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Changes in expression of podocyte-associated protein in streptozotocin-induced diabetic nephropathy. (2004)
  • Author(s): Y Kanda, Natsuki Matsumoto, S Tomioka, K Takahashi, H Akimoto, S Kakuta, H Nagoshi, T Arai, K Matsui, K Nakamura, H Kawachi, F Shimizu, S Uchida
  • Organizer: Annual meeting of Japanese Society of Nephrology
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Intrarenal localization of adiponectin receptor in streptozotocin-induced diabetic nephropathy (2004)
  • Author(s): F Takemoto, D Son, S Nakanishi, J Hoshino, N Sawa, T Tanoue, M Yokota, H Katori, Y Ubara, K Takaichi, S Hara, Y Kanda, S Uchida, Y Nakano, T kadowaki
  • Organizer: Annual meeting of Japanese Society of Nephrology
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Downregulation of the podocyte-related proteins in the mild stage of streptozotocin-induced diabetic rats. (2003)
  • Author(s): Y Kanda, N Matsumoto, M Kosuga, K Kojima, K Matsui, H Kawachi, F Shimizu, S Uchida
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国サンディエゴ
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Adiponectin binding to glomerular endothelial cells increases in diabetic rats. (2003)
  • Author(s): F Takemoto, Y Nakano, Y Kanda, M Kosuga, J Hoshino, M Yokota, H Katori, M Ubara, S Hara, K Takaichi, S Uchida
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国サンディエゴ
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Downregulation of the podocyte-related proteins in the mild stage of streptozotocin-induced diabetic rats (2003)
  • Author(s): Y Kanda, N Matsumoto, M Kosuga, K Kojima, K Matsui, H Kawachi, F Shimizu, S Uchida
  • Organizer: Annual meeting of the American Society of Nephrology
  • Place of Presentation: San Diego
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Adiponectin binding to glomerular endothelial cells increases in diabetic rats. (2003)
  • Author(s): F Takemoto, Y Nakano, Y Kanda, M Kosuga, J Hoshino, M Yokota, H Katori, M Ubara, S Kara, K Takaichi, S Uchida
  • Organizer: Annual meeting of the American Society of Nephrology
  • Place of Presentation: San Diego
  • Description: 「研究成果報告書概要(欧文)」より