Effects of adiponectin for diabetic nephropathy

脂联素对糖尿病肾病的作用

• 批准号: 18590896
• 负责人: SATOH Hiroaki
• 金额: $ 2.44万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590896/
• 关键词: Diabetic Nephropathy; Adiponectin; Resistin; アディポカイン

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.

在这项研究中，我们研究了脂联素是否会在体外和体内抑制糖尿病肾病的进展。肾小球系膜细胞增殖在进行性肾小球损伤的发病机制中起着早期和关键的作用。因此，我们首先证明脂联素抑制抵抗素诱导的DNA合成所测量的[3 H]-胸苷掺入大鼠培养的系膜细胞。与胸苷掺入的数据一致，脂联素减少了adipinin诱导的MAPK磷酸化。接下来，我们研究了脂联素对实验性糖尿病大鼠糖尿病肾病的影响，通过静脉注射腺病毒（Ad-Adipo）过表达脂联素蛋白。雄性Wistar大鼠，6周大，使用。腹腔注射链脲佐菌素（STZ）（80 mg/kg）诱导糖尿病大鼠模型。在注射STZ后10周，静脉注射Ad-lacZ或Ad-Adipo。注射Ad后3周观察脂联素对尿蛋白排泄的影响。体重、空腹血糖、空腹胰岛素、总胆固醇、高密度脂蛋白胆固醇和肌酐水平在两组间无显著差异，而尿蛋白/肌酐消耗率在两组间差异显著（P < 0. 05）。而I型和IV型胶原mRNA表达在两组间无差异。此外，Ad-Adipo组大鼠肾脏nehrin mRNA表达显著增加。Ad-Adipo组大鼠肾脏iNOS、ET-1、派-1 mRNA表达较Ad-lacZ组明显增加，eNOS mRNA表达较Ad-lacZ组明显增加，提示脂联素对糖尿病肾病有一定的预防作用，是一种潜在的治疗策略。

项目成果

The Interaction between Resistin and Adiponectin on Rat Vascular Smooth Muscle Cells Proliferation. (703-P)

抵抗素和脂联素对大鼠血管平滑肌细胞增殖的相互作用。

• 发表时间: 2008
• 作者: Hiroyuki;Hirai;Hiroaki;Satoh;Akihiro;Kudoh;Shintaroh;Nakamaki;Koji;Hasegawa;Makoto;Fujiwara;Ryo;Muraoka;Miyuki;Honma;Shinichi;Nakajima;Shigeatsu;Hashimoto;Sanae;Midorikawa;Tsuyoshi;Watanabe
• 通讯作者: Watanabe

Pioglitazone Increases Insulin Sensitivity via the Upregulation of AdipoR2 in 3T3-L1 Adipocytes. (1278-P)

吡格列酮通过上调 3T3-L1 脂肪细胞中 AdipoR2 来提高胰岛素敏感性。

• 发表时间: 2008
• 作者: Akihiro;Kudo;Hiroaki;Sato;Hiroyuki;Hirai;Shintaroh;Nakamaki;Koji;Hasegawa;Makoto;Fujiwara;Ryo;Muraoka;Miyuki;Honma;Shinichi;Nakajima;Shigeatsu;Hashimoto;Sanae;Midorikawa;Tsuyoshi;Watanabe
• 通讯作者: Watanabe

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

抵抗素对培养的系膜细胞影响的研究

• 发表时间: 2007
• 期刊: Therapeutic Research 28
• 作者: 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
• 通讯作者: 渡辺 毅

Effect of resistin in rat mesangial cells

抵抗素对大鼠系膜细胞的影响

• 发表时间: 2007
• 期刊: Therapeutic Research 28
• 作者: Hiroyuki;Hirai;Hiroaki;Satoh;Shintaro;Nakamaki;Akihiro;Kudoh;Koji;Hasegawa;Makoto;Fujiwara;Shinichi;Nakajima;Tsuyoshi;Watanabe
• 通讯作者: Watanabe

Yacon Diet Improves Hepatic Insulin Sensitivity via Reduction of TRB3 Expression in Zucker fa/fa Rats.(1528-P)

雪莲果饮食通过减少 Zucker fa/fa ​​大鼠的 TRB3 表达来提高肝脏胰岛素敏感性。(1528-P)

• 发表时间: 2007
• 作者: Hiroahi Satoh;Akihiro Kudoh;Hiroyuki Hirai;Makoto Fujiwara;Koji Hasegawa;Shinichi Nakajima;Shintaro Nakamaki;Tsuyoshi Watanabe
• 通讯作者: Tsuyoshi Watanabe