New therapeutic strategy for diabetic nephropathy

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kanazawa Medical University
• Principal Investigator: KOYA Daisuke 金沢医科大学, 医学部, 教授 (70242980)
• Project Period (FY): 2009 – 2011
• Keywords: エネルギー / 糖代謝異常 / 糖尿病腎症

Research Abstract

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.

Research Products

• [Journal Article] Emerging role of autophagy in kidney function, diseases and aging (2012)
  • Author(s): Huber TB, Edelstein CL, Hartleben B, Inoki K, Jiang M, Koya D, Kume S, Lieberthal W, Pallet N, Quiroga A, Ravichandran K, Susztak K, Yoshida S, Dong Z
  • Journal Title: Autophagy Volume: 8(7) Pages: 1-23
  • Peer Reviewed
• [Journal Article] Nutrient sensing, autophagy and diabetic nephropathy Diabetes (2012)
  • Author(s): Kume S, Thomas MC, Koya D
  • Journal Title: Jan Volume: 61(1) Pages: 23-9
  • Peer Reviewed
• [Journal Article] Autophagy as a Therapeutic Target in Diabetic Nephropathy Experimental Diabetes Research (2012)
  • Author(s): Tanaka Y, Kume S, Kitada K, Kanasaki K, Uzu T, Maegawa H, Koya D
  • Pages: 628978
  • Peer Reviewed
• [Journal Article] Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-prolin e : a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors (2011)
  • Author(s): Kanasaki M, Nagai T, Kitada M, Koya D, Kanasaki K
  • Journal Title: Fibrogenesis Tissue Repair Volume: 4 Pages: 25
  • Peer Reviewed
• [Journal Article] Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of the autophagy via restoration of Sirt1 in Diabetic Wistar fatty(fa/fa) rats, a model of type 2 diabetes (2011)
  • Author(s): Kitada M, Takeda A, Nagai T, Ito H, Kanasaki K, Koya D
  • Journal Title: Experimental Diabetes Research Pages: 908185
  • Peer Reviewed
• [Journal Article] Reversal of redox-dependent inhibition of diacylglycerol kinase by antioxidants in mesangial cells exposed to high glucose (2011)
  • Author(s): Atsumi H, Kitada M, Kanasaki K, Koya D
  • Journal Title: Mol Med Report Volume: 4(5) Pages: 923-7
  • Peer Reviewed
• [Journal Article] SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells (2011)
  • Author(s): Koyama T, Kume S, Koya D, Araki S, Isshiki K, Chin-Kanasaki M, Sugimoto T, Haneda M, Sugaya T, Kashiwagi A, Maegawa H, Uzu T
  • Journal Title: Free Radic Biol Med Volume: 51(6) Pages: 1258-67
  • Peer Reviewed
• [Journal Article] Biology of obesity : lessons from animal models of obesity (2011)
  • Author(s): Kanasaki K, Koya D
  • Journal Title: J Biomed Biotechnol Pages: 197636
  • Peer Reviewed
• [Journal Article] Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1-independent pathway (2011)
  • Author(s): Kitada M, Kume S, Imaizumi N, Koya D
  • Journal Title: Diabetes Volume: 60(2) Pages: 634-43
  • Peer Reviewed
• [Journal Article] Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney (2010)
  • Author(s): Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S, Sugimoto T, Haneda M, Kashiwagi A, Koya D
  • Journal Title: J Clin Invest Volume: 120(4) Pages: 1043-55
  • Peer Reviewed