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Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure
| Title: | Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure |
| Authors: | Ohta, Yukihiro Browse this author | | Kinugawa, Shintaro Browse this author →KAKEN DB | | Matsushima, Shouji Browse this author →KAKEN DB | | Ono, Taisuke Browse this author | | Sobirin, Mochamad A. Browse this author | | Inoue, Naoki Browse this author | | Yokota, Takashi Browse this author →KAKEN DB | | Hirabayashi, Kagami Browse this author | | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | skeletal muscle | | myocardial infarction | | apocynin |
| Issue Date: | 2011 |
| Publisher: | American Physiological Society |
| Journal Title: | American Journal of Physiology-Heart and Circulatory Physiology |
| Volume: | 300 |
| Issue: | 5 |
| Start Page: | H1637 |
| End Page: | H1644 |
| Publisher DOI: | 10.1152/ajpheart.01185.2009 |
| Abstract: | Insulin resistance has been shown to occur as a consequence of heart failure. However, its exact mechanisms in this setting remain unknown. We have previously reported that oxidative stress is enhanced in the skeletal muscle from mice with heart failure after myocardial infarction (MI) (30). This study is aimed to investigate whether insulin resistance in postinfarct heart failure is due to the impairment of insulin signaling in the skeletal muscle caused by oxidative stress. Mice were divided into four groups: sham operated (sham); sham treated with apocynin, an inhibitor of NAD(P)H oxidase activation (10 mmol/l in drinking water); MI; and MI treated with apocynin. After 4 wk, intraperitoneal insulin tolerance tests were performed, and skeletal muscle samples were obtained for insulin signaling measurements. MI mice showed left ventricular dilation and dysfunction by echocardiography and increased left ventricular end-diastolic pressure and lung weight. The decrease in glucose level after insulin load significantly attenuated in MI compared with sham. Insulin-stimulated serine phosphorylation of Akt and glucose transporter-4 translocation were decreased in MI mice by 61 and 23%, respectively. Apocynin ameliorated the increase in oxidative stress and NAD(P)H oxidase activities measured by the lucigenin assay in the skeletal muscle after MI. It also improved insulin resistance and inhibited the decrease of Akt phosphorylation and glucose transporter-4 translocation. Insulin resistance was induced by the direct impairment of insulin signaling in the skeletal muscle from postinfarct heart failure, which was associated with the enhanced oxidative stress via NAD(P)H oxidase. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/76766 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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