Inhibition of the TNF-α-Induced Serine Phosphorylation of IRS-1 at 636/639 by AICAR
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- Shibata Tomohito
- Division of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Japan
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- Takaguri Akira
- Division of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Japan
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- Ichihara Kazuo
- Division of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Japan
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- Satoh Kumi
- Division of Pharmacology, Hokkaido Pharmaceutical University School of Pharmacy, Japan
書誌事項
- タイトル別名
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- Inhibition of the TNF-<i>α</i>–Induced Serine Phosphorylation of IRS-1 at 636/639 by AICAR
- Inhibition of the TNF-α^|^ndash;Induced Serine Phosphorylation of IRS-1 at 636/639 by AICAR
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抄録
AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling. However, the mechanism by which AMPK regulates insulin signaling remains unclear. Serine phosphorylation of insulin receptor substrate (IRS)-1 negatively regulates insulin signaling. Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes. We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α–induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal–regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation. In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis. Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue. In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α–induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4. Taken together, these findings provide evidence that AMPK plays a crucial role in improving of type 2 diabetes.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 122 (2), 93-102, 2013
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205180967424
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- NII論文ID
- 10031185401
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- NII書誌ID
- AA11806667
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- COI
- 1:STN:280:DC%2BC3snmtVCktA%3D%3D
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 024637811
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- PubMed
- 23698110
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可