Signaling axis of urotensin II, parasympathetic nerves, and nitric oxide on carbohydrate metabolism: A clinical
| Project/Area Number | 17590912 |
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
TAMURA Akira Tohoku University, Hospital, Research Associate, 病院, 助手 (00375023)
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| Co-Investigator(Kenkyū-buntansha) |
HINOKIO Yoshinori Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (10282071)
SUZUKI Susumu Tohoku University, Graduate School of Medicine, Lecturer, 大学院医学系研究科, 講師 (70216399)
ISHIHARA Hisamitsu Tohoku University Hospital, Research Associate, 病院・講師 (60361086)
高橋 和眞 東北大学, 病院・助手 (60292215)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed(Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2006 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2005 : ¥2,200,000 (Direct Cost : ¥2,200,000)
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| Keywords | Diabetes / Urotensin II / Parasympatic nerve / Nitric Oxide / Insulin / Liver / Gene knockdown |
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| Research Abstract |
We reported that genetic polymorphisms of urotensin II, UTS2, one of most potent vasoactive polypeptides, might be contributed to in vivo insulin sensitivity, resulting to the onset of diabetes.
To elucidate possible roles of urotensin II on insulin sensitivity and glucose tolerance, we developed B6 mice (UT2-mice) that over-expressed UT2 in mice liver by the administration of adenovirus vector containing UT2 via tail veins, and investigate glucose intolerance and insulin sensitivity as compared with the B6 mice (LacZ-mice) that over-expressed LacZ in liver by the application of adenovirus vector containing LacZ.
We found a significant improvement of insulin sensitivity and glucose tolerance in UT2-mice, as compared with LacZ-mice. Then, we developed B6 mice (GPR14-mice) that over-expressed GPR14 in mice liver by the Ladministration of adenovirus vector containing GPR14. We also confirmed a significant improvement of insulin sensitivity and glucose tolerance in UT2-mice, as compared with LacZ-mice. We concluded that the activation of urorensin II signaling in liver contributed to the improvement of insulin sensitivity and glucose tolerance.
There were accumulating evidence suggesting that the signaling of parasympathetic nerve to NO regulates insulin signaling on glycogen synthesis, gluconeogenesis, lipogenesis and anti-lipolysis. We confirmed the enhanced signaling pathway of parasympathetic nerve to NO in UT2-mice and GPR14-mice, as compared with LacZ-mice. Thus, this investigation clearly demonstrated that signaling defects of urotensin II, parasympathetic nerve to NO might be one of pathogenic mechanisms of insulin resistance and diabetes.
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Report
(3results)
Research Products
(17results)
