| Item type |
文献 / Documents(1) |
| 公開日 |
2025-03-06 |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1074/jbc.M111.228817 |
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関連名称 |
10.1074/jbc.M111.228817 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Influence of the Hepatic Eukaryotic Initiation Factor 2α (eIF2α) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism |
| タイトル別表記 |
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その他のタイトル |
ER Stress and Insulin Resistance |
| 著者 |
Birkenfeld, Andreas L.
Lee, Hui-Young
Majumdar, Sachin
Jurczak, Michael J.
Camporez, Joao Paulo
Jornayvaz, Francois R.
Frederick, David W.
Guigni, Blas
Kahn, Mario
Zhang, Dongyang
Weismann, Dirk
Arafat, Ayman M.
Pfeiffer, Andreas F.
Lieske, Stefanie
親泊, 政一
Ron, David
Samuel, Varman T.
Shulman, Gerald I.
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| 抄録 |
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内容記述 |
Recent studies have implicated endoplasmic reticulum (ER) stress in insulin resistance associated with caloric excess. In mice placed on a 3-day high fat diet, we find augmented eIF2α signaling, together with hepatic lipid accumulation and insulin resistance. To clarify the role of the liver ER stress-dependent phospho-eIF2α (eIF2α-P) pathway in response to acute caloric excess on liver and muscle glucose and lipid metabolism, we studied transgenic mice in which the hepatic ER stress-dependent eIF2α-P pathway was inhibited by overexpressing a constitutively active C-terminal fragment of GADD34/PPP1R15a, a regulatory subunit of phosphatase that terminates ER stress signaling by phospho-eIF2α. Inhibition of the eIF2α-P signaling in liver led to a decrease in hepatic glucose production in the basal and clamped state, which could be attributed to reduced gluconeogenic gene expression, resulting in reduced basal plasma glucose concentrations. Surprisingly, hepatic eIF2α inhibition also impaired insulin-stimulated muscle and adipose tissue insulin sensitivity. This latter effect could be attributed at least in part by an increase in circulating IGFBP-3 levels in the transgenic animals. In addition, infusion of insulin during a hyperinsulinemic-euglycemic clamp induced conspicuous ER stress in the 3-day high fat diet-fed mice, which was aggravated through continuous dephosphorylation of eIF2α. Together, these data imply that the hepatic ER stress eIF2α signaling pathway affects hepatic glucose production without altering hepatic insulin sensitivity. Moreover, hepatic ER stress-dependent eIF2α-P signaling is implicated in an unanticipated cross-talk between the liver and peripheral organs to influence insulin sensitivity, probably via IGFBP-3. Finally, eIF2α is crucial for proper resolution of insulin-induced ER stress. |
| 書誌情報 |
en : Journal of Biological Chemistry
巻 286,
号 42,
p. 36163-36170,
発行日 2011-08-05
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| 収録物ID |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1083351X |
| 収録物ID |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
00219258 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA1202441X |
| 出版者 |
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出版者 |
American Society for Biochemistry and Molecular Biology |
| 出版者 |
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出版者 |
Elsevier |
| 権利情報 |
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|
権利情報 |
This is an Open Access article under the CC BY license. |
| EID |
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|
識別子 |
234192 |
| 言語 |
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|
言語 |
eng |
jbc_286_42_36163.pdf (1.1 MB)
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