論文 - 詳細
| RRC ID | 64420 |
|---|---|
| 著者 | Kanda T, Wakino S, Homma K, Yoshioka K, Tatematsu S, Hasegawa K, Takamatsu I, Sugano N, Hayashi K, Saruta T. |
| タイトル | Rho-kinase as a molecular target for insulin resistance and hypertension. |
| ジャーナル | FASEB J |
| Abstract |
Rho-kinase plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of insulin receptor substrate-1 (IRS-1) in cultured vascular smooth muscle cells. We therefore examined the role of Rho-kinase in the development of insulin resistance in Zucker obese rats. In skeletal muscles and aortic tissues of Zucker obese rats, activation of RhoA/Rho-kinase was observed. Long-term Rho-kinase inhibition by 4 wk treatment with fasudil (a Rho-kinase inhibitor) not only reduced blood pressure but corrected glucose and lipid metabolism, with improvement in serine phosphorylation of IRS-1 and insulin signaling in skeletal muscles. Direct visualization of skeletal muscle arterioles with an intravital CCD videomicroscope demonstrated that both acetylcholine- and sodium nitroprusside-induced vasodilations were blunted, which were restored by the fasudil treatment. Furthermore, both fasudil and Y-27632 prevented the serine phosphorylation of IRS-1 induced by insulin and/or tumor necrosis factor-alpha in skeletal muscle cells. Collectively, Rho-kinase is responsible for the impairment of insulin signaling and may constitute a critical mediator linking between metabolic and hemodynamic abnormalities in insulin resistance. |
| 巻・号 | 20(1) |
| ページ | 169-71 |
| 公開日 | 2006-1-1 |
| DOI | 10.1096/fj.05-4197fje |
| PII | 05-4197fje |
| PMID | 16267124 |
| MeSH | 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / metabolism 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology Acetylcholine Animals Arterioles / drug effects Cell Line Glucose Tolerance Test Hypertension / drug therapy* Insulin / metabolism Insulin Resistance / physiology* Intracellular Signaling Peptides and Proteins Muscle, Skeletal / blood supply Nitroprusside Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / metabolism* Protein Transport Rats Rats, Zucker Signal Transduction Tumor Necrosis Factor-alpha / metabolism rho-Associated Kinases rhoA GTP-Binding Protein / metabolism |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |