WEKO3
アイテム
Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance
http://hdl.handle.net/10295/3128
http://hdl.handle.net/10295/3128290aacc6-fd3c-4b8c-ac41-bab4b43777a0
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
内容要旨及び審査結果要旨 (401.7 kB)
|
|
|
|
本文 (3.0 MB)
|
|
| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2016-06-22 | |||||
| タイトル | ||||||
| タイトル | Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 別タイトル | ||||||
| その他のタイトル | 肝臓のMEK1シグナル伝達系の阻害はインスリン抵抗性を改善する | |||||
| 作成者 |
植山, 篤則
× 植山, 篤則× UEYAMA, Atsunori |
|||||
| 内容記述（抄録） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Although mitogen-activated protein kinase kinase (MEK) is a key signaling molecule and a negative regulator of insulin action, it is still uncertain whether MEK can be a therapeutic target for amelioration of insulin resistance (IR) in type 2 diabetes (T2D) in vivo. To clarify whether MEK inhibition improves T2D, we examined the effect of continuous MEK inhibition with two structurally different MEK inhibitors, RO5126766 and RO4987655, in mouse models of T2D. RO5126766 and RO4987655 were administered via dietary admixture. Both compounds decreased blood glucose and improved glucose tolerance in doses sufficient to sustain inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation downstream of MEK in insulin-responsive tissues in db/db mice. A hyperinsulinemic-euglycemic clamp test showed increased glucose infusion rate (GIR) in db/db mice treated with these compounds, and about 60% of the increase was attributed to the inhibition of endogenous glucose production, suggesting that the liver is responsible for the improvement of IR. By means of adenovirus-mediated Mek1 shRNA expression, we confirmed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice. Taken together, these results suggested that the MEK signaling pathway could be a novel therapeutic target for novel antidiabetic agents. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 書誌情報 | 発行日 2016-06-01 | |||||
| 出版者 | ||||||
| 出版者 | 秋田大学 | |||||
| 備考 | ||||||
| 値 | 秋田大学審査学位論文(Journal of Diabetes Research,2016掲載論文) | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 11401 | |||||
| 学位授与機関名 | 秋田大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2016-03-28 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 乙第639号 | |||||
