| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Diabetes mellitus and insulin resistance are associated with a variety of adverse cardiovascular events, and to treat such vascular complication, it is important to improve insulin sensitivity and vascular dysfunction. I found: (i) that the GRK2/eNOS, and IRS/PTP1B/eNOS plays important roles in endothelium-derived relaxation and NO production in the artery, (ii) that the impaired NO production in endothelial cells that I detected in insulin-resistance model or type 2 diabetic models may be attributable to a reduced Akt/eNOS activity, which in turn may result from a enhanced GRK2 activity and an abnormal platelets. Moreover, AT1 receptor-antagonist, PTP1B inhibitor, and GRK2 inhibitor normalized endothelial function. I also found that the Up4A- and 5-HT -induced contraction is augmented in insulin-resistance models. This augmentation may be due to smooth muscle activation mediated by SERT, Rho kinase and COX/TP receptor signaling.
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