New therapeutic strategy for diabetic nephropathy

糖尿病肾病治疗新策略

• 批准号: 21591148
• 负责人: KOYA Daisuke
• 金额: $ 2.91万
• 依托单位: Kanazawa 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: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591148/
• 关键词: エネルギー; 糖代謝異常; 糖尿病腎症; レスベラトロール; カロリー制限; プロテオーム解析; オートファジー; ミトコンドリア; 酸化ストレス; 加齢腎; Mn-SOD

Here, we hypothesized that mitochondria dysfunction due to aging-and diabetes-induced sirtuin 1(SIRT1) down regulation could result in renal inflammation, increased oxidative stress, and finally renal pathologies. Firstly, calorie restriction exerts anti-inflammatory effects and improves the dysregulation of autophagy through the restoration of SIRT1 in the aging kidneys, resulting in the amelioration of renal injuries. Secondly, resveratrol(RSV) ameliorates renal injury and enhanced mitochondrial biogenesis with Mn-SOD dysfunction in the kidney of db/db mice, through improvement of oxidative stress via normalization of Mn-SOD function and glucose-lipid metabolism via AMPK/SIRT1-independent pathway. Thirdly, calorie restriction exerts anti-inflammatory effects and improves the dysregulation of autophagy through the restoration of SIRT1 in the kidneys of WFRs, resulting in the amelioration of renal injuries in type 2 diabetes.

在这里，我们假设由于衰老和糖尿病诱导的Sirtuin 1（SIRT1）降低的线粒体功能障碍可能导致肾脏炎症，氧化应激增加，最后会导致肾脏病理。首先，卡路里限制会发挥抗炎作用，并通过恢复衰老肾脏中的SIRT1来改善自噬的失调，从而减轻肾脏损伤。其次，白藜芦醇（RSV）通过改善MN-SOD功能和葡萄糖 - 脂质函数和通过AMPK/SIRTSIRT1-依赖性的葡萄糖 - 依赖性的代谢性来改善氧化应激，从而改善DB/DB小鼠肾脏中Mn-SOD功能障碍的线粒体生物发生。第三，卡路里限制会产生抗炎作用，并通过恢复WFR肾脏的SIRT1来改善自噬的失调，从而改善2型糖尿病中肾脏损伤的改善。

项目成果

Sirt1による老化腎障害における虚血応答制御

Sirt1 对衰老肾损伤缺血反应的调节

• 发表时间: 2010
• 作者: Nagare T;Sakaue H;et al;Liang F;古家大祐
• 通讯作者: 古家大祐

Effectiveness of Calorie restriction on Ameliorating Diabetic Nephropathy possibly through its anti-inflammatory action

热量限制可能通过其抗炎作用改善糖尿病肾病的有效性

• 发表时间: 2010
• 作者: 小田邊修一;橋永俊彦;原暁紅;福谷知香;大木剛;柿野聡美;和田暢彦;栗田弥生;中山ひとみ;田尻祐司;下川功;山田研太郎;KOYA D
• 通讯作者: KOYA D

SIRT1, a calorie restriction mimetic, in a new therapeutic approach for type 2 diabetes mellitus and diabetic vascular complications.

• DOI: 10.2174/187153010790827957
• 发表时间: 2010-02
• 期刊: Endocrine, metabolic & immune disorders drug targets
• 作者: S. Kume;T. Uzu;A. Kashiwagi;D. Koya

Reversal of redox-dependent inhibition of diacylglycerol kinase by antioxidants in mesangial cells exposed to high glucose

• DOI: 10.3892/mmr.2011.524
• 发表时间: 2011-09-01
• 期刊: MOLECULAR MEDICINE REPORTS
• 影响因子: 3.4
• 作者: Atsumi, Hisanari;Kitada, Munehiro;Koya, Daisuke
• 通讯作者: Koya, Daisuke

Emerging role of autophagy in kidney function, diseases and aging

• DOI: 10.4161/auto.19821
• 发表时间: 2012-07-01
• 期刊: AUTOPHAGY
• 影响因子: 13.3
• 作者: Huber, Tobias B.;Edelstein, Charles L.;Dong, Zheng
• 通讯作者: Dong, Zheng