2005 Fiscal Year Final Research Report Summary
Role of adiponectin and its binding to the glomeruli in development and progression of diabetic nephropathy
| Project/Area Number |
16590800
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Teikyo University |
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Principal Investigator |
UCHIDA Shunya Teikyo University, 医学部, 教授 (50151882)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Diabetic nephropathy / Nephrin / α3-integrin / α-dystroglycan / Adiponectin / Endothelial cell / Mesangial cell / Double immunostaining |
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| 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
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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. Less
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Research Products
(10 results)
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[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
Year and Date
20040600
Description
「研究成果報告書概要(和文)」より
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[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
Year and Date
20040600
Description
「研究成果報告書概要(和文)」より
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[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
Year and Date
20040600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Intrarenal localization of adiponectin receptor in streptozotocin-induced diabetic nephropathy2004
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
Year and Date
20040600
Description
「研究成果報告書概要(欧文)」より
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[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
Year and Date
20031100
Description
「研究成果報告書概要(和文)」より
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[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
Year and Date
20031100
Description
「研究成果報告書概要(欧文)」より
