Effects of adiponectin for diabetic nephropathy

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: SATOH Hiroaki Fukushima Medical University, School of Medicine, Assistant Professor (20323595)
• Co-Investigator(Kenkyū-buntansha): WATANABE Tsuyoshi Fukushima Medical University, School of Medicine, Professor (80158641)
• Project Period (FY): 2006 – 2007
• Keywords: Diabetic Nephropathy / Adiponectin / Resistin

Research Abstract

In this study, we investigated whether adiponectin would inhibit the progression of diabetic nephropathy in vitro and in vivo. The mesangial cell proliferation appears to play an early and pivotal role in the pathogenesis of progressive glomerular injury. Therefore, we first demonstrated the adiponectin inhibited resistin-induced DNA synthesis as measured by [3H]-thymidine incorporation on rat cultured mesangial cells. Consistent with the thymidine incorporation data, adiponectin diminished the resistin induced phosphorylation of MAPK.
Next, we investigated the effect of adiponectin on diabetic nephropathy in experimental diabetic rats by overexpression the adipinectin protein using intravenous administration of an adenovirus (Ad-Adipo). Male Wistar rats,. 6-week-old, were used. Diabetic rat was induced by intraperitoneal injection of streptozotocin (STZ) (80 mg/kg) in citrate buffer (pH 4.5). At 10 weeks after the STZ injection, Ad-lacZ or Ad-Adipo was injected intravenous. The effects of adiponectin on urinary protein excretion were observed after 3 weeks post Ad injection. Body weight, plasma fasting glucose levels, plasma fasting insulin levels, total cholesterol levels, HDL-cholesterol levels, and plasma creatinine levels are no difference between two groups, whereas and urinary protein/creatinine exertion ratio levels were significantly determined by 25%.
In kidney, TGF-a mRNA expression was significantly decreased in the Ad-Adipo rats compared with Ad-lacZ rats, whereas collagen type I and IV mRNA expression were no difference between two groups. In addition, nehrin mRNA expression in kidney was significantly increased in the Ad-Adipo rats. Interestingly, iNOS, ET-1, and PAI-1 mRNA expression were significantly increased, whereas eNOS mRNA expression was in kidney with the ad-Adipo rats compared with Ad-lacZ rats.
These results suggest a role of adiponectin in the prevention of diabetic nephropathy and show that adiponectin is a potential therapeutic strategy.

Research Products

• [Journal Article] レジスチンの培養メサンギウム細胞における影響についての検討 (2007)
  • Author(s): 平井 裕之, 佐藤 博亮, 中牧 慎太郎, 工藤 明宏, 長谷川 浩司, 藤原 淳, 中嶋 真一, 渡辺 毅
  • Journal Title: Therapeutic Research 28 Pages: 1896
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effect of resistin in rat mesangial cells (2007)
  • Author(s): Hiroyuki, Hirai, Hiroaki, Satoh, Shintaro, Nakamaki, Akihiro, Kudoh, Koji, Hasegawa, Makoto, Fujiwara, Shinichi, Nakajima, Tsuyoshi, Watanabe
  • Journal Title: Therapeutic Research 28 Pages: 1896
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Pioglitazone Increases Insulin Sensitivity via the Upregulation of AdipoR2 in 3T3-L1 Adipocytes.(1278-P) (2008)
  • Author(s): Akihiro Kudo, Hiroaki Sato, Hiroyuki Hirai, Shintaroh Nakamaki, Koji Hasegawa, Makoto Fujiwara, Ryo Muraoka, Miyuki Honma, Shinichi Nakjima, Shigeatsu Hashimoto, Sanae Midorikawa, Tsuyoshi Watanabe
  • Organizer: 68th American Diabetes Association Scientific Sessions
  • Place of Presentation: San Francisco,CA.,USA
  • Year and Date: 20080606-10
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The Interaction between Resistin and Adiponectin on Rat Vascular Smooth Muscle Cells Proliferation.(703-P) (2008)
  • Author(s): Hiroyuki Hirai, Hiroaki Satoh, Akihiro Kudoh, Shintaroh Nakamaki, Koji Hasegawa, Makoto Fujiwara, Ryo Muraoka, Miyuki Honma, Shinichi Nakajima, Shigeatsu Hashimoto, Sanae Midorikawa, Tsuyoshi Watanabe
  • Organizer: 68th American Diabetes Association Scientific Sessions
  • Place of Presentation: San Francisco,CA.,USA
  • Year and Date: 20080606-10
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Pioglitazone Increases Insulin Sensitivity via the Upregulation of AdipoR2 in 3T3-L1 Adipocytes. (1278-P) (2008)
  • Author(s): Akihiro, Kudo, Hiroaki, Sato, Hiroyuki, Hirai, Shintaroh, Nakamaki, Koji, Hasegawa, Makoto, Fujiwara, Ryo, Muraoka, Miyuki, Honma, Shinichi, Nakajima, Shigeatsu, Hashimoto, Sanae, Midorikawa, Tsuyoshi, Watanabe
  • Organizer: 68th American Diabetes Association Scientific Sessions.
  • Place of Presentation: San Francisco, CA., USA
  • Year and Date: 20080606-10
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The Interaction between Resistin and Adiponectin on Rat Vascular Smooth Muscle Cells Proliferation. (703-P) (2008)
  • Author(s): Hiroyuki, Hirai, Hiroaki, Satoh, Akihiro, Kudoh, Shintaroh, Nakamaki, Koji, Hasegawa, Makoto, Fujiwara, Ryo, Muraoka, Miyuki, Honma, Shinichi, Nakajima, Shigeatsu, Hashimoto, Sanae, Midorikawa, Tsuyoshi, Watanabe
  • Organizer: 68th American Diabetes Association Scientific Sessions.
  • Place of Presentation: San Francisco, CA., USA
  • Year and Date: 20080606-10
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Yacon Diet Improves Hepatic Insulin Sensitivity via Reduction of TRB3 Expression in Zucker fa/fa Rats.(1528-P) (2007)
  • Author(s): Hiroahi Satoh, Akihiro Kudoh, Hiroyuki Hirai, Makoto Fujiwara, Koji Hasegawa, Shinichi Nakajima, Shintaro Nakamaki, Tsuyoshi Watanabe
  • Organizer: 67th American Diabetes Association Scientific Sessions
  • Place of Presentation: Chicago,IL,USA
  • Year and Date: 20070622-26
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Yacon Diet Improves Hepatic Insulin Sensitivity via Reduction of TRB3 Expression in Zucker fa/fa Rats. (1528-P) (2007)
  • Author(s): Hiroaki, Satoh, Akihiro, Kudoh, Hiroyuki, Hirai, Makoto, Fujiwara, Koji, Hasegawa, Shinichi, Nakajima, Shintaro, Nakamaki, Tsuyoshi, Watanabe
  • Organizer: 67th American Diabetes Association Scientific Sessions
  • Place of Presentation: in Chicago, IL., USA
  • Year and Date: 20070622-26
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Adiponectin Improves Free-Fatty Acid-Induced Insulin Resistance in Estrogen-Deficient, Insulin Resistant Female Wistar Rats.(1466-P) (2006)
  • Author(s): Himaki Satoh, MT Audrey Nguyen, Tsuyosbi Watanabe, Jerrold M Olefsky
  • Organizer: 66th Alnehcan Diabetes Association Scientific Sessions
  • Place of Presentation: Washington,D.C,USA
  • Year and Date: 20060609-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The Interaction among Resistin, TNF-alpha, and Adiponectin on Glucose Transport in 3T3-L1 Adipocytes.(31-LB) (2006)
  • Author(s): Akihiro Kudoh, Hiroaki Satoh, Hiroyuki Hirai, Koji Hasegawa, Makoto Fujiwara, Shinichi Nakajima, Tsuyoshi Watanabe
  • Organizer: 66th American Diabetes Association Scientific Sessions
  • Place of Presentation: Washington D.C,USA
  • Year and Date: 20060609-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Adiponectin Improves Free-Fatty Acid-Induced Insulin Resistance in Estrogen-Deficient, Insulin Resistant Female Wistar Rats. (1466-P) (2006)
  • Author(s): Hiroaki, Satoh, MT, Audrey, Nguyen, Tsuyoshi, Watanabe, Jerrold, M., Olefsky
  • Organizer: 66th American Diabetes Association Scientific Sessions.
  • Place of Presentation: in Washington, D.C., USA
  • Year and Date: 20060609-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The Interaction among Resistin, TNF-alpha, and Adiponectin on Glucose Transport in 3T3-L1 Adipocytes. (31-LB) (2006)
  • Author(s): Akihiro, Kudoh, Hiroaki, Satoh, Hiroyuki, Hirai, Koji, Hasegawa, Makoto, Fujiwara, Shinichi, Nakajima, Tsuyoshi, Watanabe
  • Organizer: 66th American Diabetes Association Scientific Sessions.
  • Place of Presentation: in Washington, D.C., USA
  • Year and Date: 20060609-13
  • Description: 「研究成果報告書概要(欧文)」より