Role of mitochondrial ROS generation in the development of diabetic complications

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Department of Clinical Research, Nationai Hospital Organization Kumamoto Medical Center (2015-2016); Kumamoto University (2014)
• Principal Investigator: Nishikawa Takeshi 独立行政法人国立病院機構熊本医療センター(臨床研究部), 独立行政法人国立病院機構熊本医療センター(臨床研究部), 診療科医長 (70336212)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糖尿病 / 糖尿病合併症 / 活性酸素

Outline of Final Research Achievements

We previously proposed that hyperglycemia-induced mitochondrial ROS (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by manganese superoxide dismutase (MnSOD) overexpression. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Thus, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

Free Research Field

医歯薬学