Crosstalk of endothelin-1 and adipokine in diabetic complications
| Project/Area Number |
18590245
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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 |
General pharmacology
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| Research Institution | Hoshi University |
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Principal Investigator |
KAMATA Katsuo Hoshi University, Faculty of Pharm. Sci., Ph.D. Professor (40121496)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | diabetes / endothelin-1 / AP-1 / NAD(P) H oxidase / endothelium / AMPK / adiponectin / EDHF / スーパーオキシド / アデポィネクチン / インスリン / thromoxane A2 / 合併症 / NAD(P)H oxidase / PPARγ / スーパーオキサイド |
|---|
| Research Abstract |
By this grant, I obtained following data.
1) In untreated STZ rats,(1) ACh-induced relaxation, cGMP accumulation,(2) aortic superoxide generation, nitrotyrosine expression, and NAD(P) H oxidase activity were increased ;(3) plasma endothelin-1(ET-1) and aortic c-Jun(AP-1 component) protein expressions were increased. Pioglitazone treatment markedly corrected the above abnormalities. These results suggest that pioglitazone treatment improves endothelium-dependent relaxation by reducing oxidative stress via increased SOD activity, decreased NAD(P) H oxidase activity, and a decreased ET-1 level, and that this decreased ET-1 level may be attributable to an inhibition of the AP-1 signaling pathway.
2) In acute studies on OLETF mesenteric arteries, the ACh-induced relaxation was impaired and the relaxation became weaker at high ACh concentrations. Both metformin and AICAR(an activator of AMP-kinase(AMPK), which is also activated by metformin) suppressed both the ACh-induced EDCF-mediated contraction and the ACh-stimulated production of prostanoids(TXA2 and PGE2). Metformin treatment :(a) improved the ACh-induced NO-or EDHF-mediated relaxation and COX-mediated contraction,(b) reduced the EDCF-mediated contraction, and(c) suppressed the production of prostanoids. These results suggest that metformin improves endothelial functions in OLETF mesenteric arteries by suppressing vasoconstrictor prostanoids(at least partly via sustained AMPK activation).
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Report
(3 results)
Research Products
(47 results)
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[Journal Article] Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed2006
Author(s)
Kamata, K., Makino, A., Kanie, N., Oda, S., Matsumoto, T., Kobayashi, T., Kikuchi, T., Nishimura, M. And Honda, T
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Journal Title
J.Smooth Muscle Res 42
Pages: 75-88
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Enhancement of methoxamine-induced contractile responses of rat ventricular muscle in streptozotocin-induced diabetes is associated with alphalA adrenoceptor upregulation2006
Author(s)
Kamata, K., Satoh, T., Matsumoto, T., Nogucbi, E., Taguchi, K., Kobayashi, T., Tanaka, H. And Shigenobu, K.
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Journal Title
Acta.Physiol (Oxf) 188
Pages: 173-183
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Effects of anthocyanidin derivative(HK-008) on relaxation in rat perfused mesenterial bed.2006
Author(s)
Kamata, K., Makino, A., Kanie, N., Oda, S., Matsumoto, T., Kobayashi, T., Kikuchi, T., Nishimura, M., Honda, T.
-
Journal Title
J. Smooth Muscle Res 42
Pages: 75-88
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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-
[Journal Article] Enhancement of methoxamine-induced contractile responese of rat ventricular muscle in streptozotocin-induced diabetes is associated with alphalA adrenoceptor upregulation.2006
Author(s)
Kamata, K., Satoh, T., Matsumoto, T., Noguchi, E., Taguchi, K., Kobayashi, T., Tanaka, H., Shigenobu, K.
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Journal Title
Acta. Physiol(Oxf) 188
Pages: 173-183
Description
「研究成果報告書概要(欧文)」より
Related Report
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