Identification of molecular mechanisms related to the development of insulin resistance in microvascular endothelial cell
| Project/Area Number |
24590127
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| 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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| Keywords | 血管 / 糖尿病 / インスリン抵抗 |
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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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Report
(4 results)
Research Products
(36 results)
