| Item type |
文献 / Documents(1) |
| 公開日 |
2025-02-21 |
| 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/10.1186/1475-2840-11-139 |
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関連名称 |
10.1186/1475-2840-11-139 |
| 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 |
Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice |
| 著者 |
Shiota, Asuka
島袋, 充生
福田, 大受
添木, 武
Sato, Hiromi
Uematsu, Etsuko
Hirata, Yoichiro
黒部, 裕嗣
Maeda, Norikazu
阪上, 浩
Masuzaki, Hiroaki
Shimomura, Iichiro
佐田, 政隆
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| 抄録 |
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内容記述 |
Background: Telmisartan is a well-established angiotensin II type 1 receptor blocker that improves insulin sensitivity in animal models of obesity and insulin resistance, as well as in humans. Telmisartan has been reported to function as a partial agonist of the peroxisome proliferator-activated receptor (PPAR) γ, which is also targeted by the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase (SIRT1). Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo.
Methods: Nine-week-old male db/db mice were fed a 60% high-fat diet, with orally administrated either vehicle (carboxymethyl-cellulose, CMC), 5 mg/kg telmisartan, or 5 mg/kg telmisartan and 1 mg/kg GW9662, a selective irreversible antagonist of PPARγ, for 5 weeks. Effects of telmisartan on Sirt1 mRNA, AMPK phosphorylation, and NAD+/NADH ratio were determined in C2C12 cultured myocytes.
Results and discussion: Telmisartan treatment improved insulin sensitivity in obese db/db mice fed a high-fat diet and led to reduction in the size of hypertrophic pancreatic islets in these mice. Moreover, in vitro treatment with telmisartan led to increased expression of Sirt1 mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in AMPK phosphorylation, an increase in NAD+/NADH ratio, and increases in the mRNA levels of PGC1α, FATP1, ACO, and GLUT4.
Conclusions: Our results indicate that telmisartan acts through a PPARγ-independent pathway, but at least partially exerts its effects by acting directly on skeletal muscle AMPK/SIRT1 pathways. |
| キーワード |
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|
主題 |
Adiponectin |
| キーワード |
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|
主題 |
AMP-activated protein kinase |
| キーワード |
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|
主題 |
Obesity |
| キーワード |
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|
主題 |
Peroxisome proliferator-activated receptor-γ |
| キーワード |
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|
主題 |
SIRT1 |
| 書誌情報 |
en : Cardiovascular Diabetology
巻 11,
p. 139,
発行日 2012-11-08
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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 |
14752840 |
| 出版者 |
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出版者 |
BioMed Central |
| 出版者 |
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|
出版者 |
Springer Nature |
| 権利情報 |
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|
権利情報 |
This is an Open Access article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| EID |
|
|
識別子 |
257847 |
| 言語 |
|
|
言語 |
eng |
cardiab_11_139.pdf (1 MB)
