論文 - 詳細
| RRC ID | 37705 |
|---|---|
| 著者 | Iwasaki Y, Nishiyama M, Taguchi T, Asai M, Yoshida M, Kambayashi M, Terada Y, Hashimoto K. |
| タイトル | Insulin exhibits short-term anti-inflammatory but long-term proinflammatory effects in vitro. |
| ジャーナル | Mol Cell Endocrinol |
| Abstract |
Although insulin is indispensable for maintaining glucose homeostasis, it is still controversial whether or not a high concentration of insulin is deleterious. We examined the effect of insulin on the transcriptional activity of NF-kappaB, which mediates the expression of a variety of inflammation/coagulation-related genes using hepatocyte cell lines in vitro. We found that insulin (1 nM) alone caused minimal increase in NF-kappaB-mediated transcription. On the other hand, when cells were simultaneously treated with proinflammatory cytokines such as TNFalpha, the following dual effect of insulin was observed: short-term (6h) suppressive, and long-term (36 h or later) stimulatory effects. The former effect was transient and appears to be mediated by the phosphatidylinositol 3 kinase (PI(3)K) signaling pathway. The latter effect, in contrast, was more pronounced, enhancing the TNFalpha-stimulated NF-kappaB-dependent transcription by more than sevenfold. This positive effect was NF-kappaB-specific, and was eliminated by mitogen-activated protein kinase (MAPK) inhibitors. Altogether, our data suggest that insulin has short-term anti-inflammatory but long-term proinflammatory effects. From a clinical standpoint, this implies that low basal and periodically high plasma insulin is beneficial, whereas a sustained rise in plasma insulin, as often seen in patients with obesity, may induce atherothrombotic disorders, because of the NF-kappaB-mediated overexpression of proinflammatory/procoagulant/antifibrinolytic proteins in the liver. |
| 巻・号 | 298(1-2) |
| ページ | 25-32 |
| 公開日 | 2009-1-27 |
| DOI | 10.1016/j.mce.2008.09.030 |
| PII | S0303-7207(08)00419-X |
| PMID | 18955107 |
| MeSH | Anti-Inflammatory Agents / pharmacology Humans Hypoglycemic Agents / pharmacology Inflammation / chemically induced* Inflammation / genetics Inflammation / prevention & control* Inflammation Mediators / pharmacology Insulin / pharmacology* Liver / drug effects Liver / metabolism Models, Biological NF-kappa B / genetics NF-kappa B / metabolism Receptor, Insulin / genetics Receptor, Insulin / metabolism Signal Transduction / drug effects Signal Transduction / genetics Time Factors Transcription, Genetic Tumor Cells, Cultured |
| IF | 3.871 |
| 引用数 | 21 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| 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 | X(Twitter) |
| 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 | HuH-7(RCB136) |