| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Research Abstract |
We investigated whether frequent hypoglycemic episodes increase susceptibility to ischemia/reperfusion in diabetic rat heart and involvement of microRNA (miRNA). Cultured cardiomyocytes were alternately exposed to high (450mg/dL) or low (30mg/dL) glucose concentrations for 5 days. Glucose fluctuations increased levels of reactive oxygen species (ROS) and rendered cardiomyocytes more vulnerable to oxidative stress. For the study in vivo, diabetes mellitus was induced by intravenous injection of streptozotocin and glucose fluctuation was induced by 24-h- fast and insulin injection. Isolated hearts were exposed to 20-min global ischemia/30-min reperfusion. The infarcts were larger in the hearts with glucose fluctuations. Electron microscopy revealed swollen mitochondria with destroyed cristae in diabetic heart, and glucose fluctuations aggravated these changes. Levels of ROS were also increased, and catalase and superoxide dismutase activities were down-regulated by glucose fluctuations. We explored the expression profiles of miRNAs using microarray analysis. The expressions of two miRNAs were more abundant in the hearts exposed to glucose fluctuations. These miRNAs appeared to contribute to decreased activities of antioxidant enzymes and subsequent ROS increase. Fluctuating glucose levels increased ROS generation and enhanced ischemia/reperfusion injury in the diabetic heart. Up-regulated miRNAs might account for the increased ROS by suppressing antioxidant enzymes.
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