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Angiotensin II receptor blocker improves the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice

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Title: Angiotensin II receptor blocker improves the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice
Authors: Takada, Shingo Browse this author →KAKEN DB
Kinugawa, Shintaro Browse this author →KAKEN DB
Hirabayashi, Kagami Browse this author
Suga, Tadashi Browse this author
Yokota, Takashi Browse this author →KAKEN DB
Takahashi, Masashige Browse this author
Fukushima, Arata Browse this author →KAKEN DB
Homma, Tsuneaki Browse this author
Ono, Taisuke Browse this author
Sobirin, Mochamad A. Browse this author
Masaki, Yoshihiro Browse this author
Mizushima, Wataru Browse this author
Kadoguchi, Tomoyasu Browse this author
Okita, Koichi Browse this author →KAKEN DB
Tsutsui, Hiroyuki Browse this author →KAKEN DB
Keywords: oxidative stress
Issue Date: 2013
Publisher: American Physiological Society
Journal Title: Journal of Applied Physiology
Volume: 114
Issue: 7
Start Page: 844
End Page: 857
Publisher DOI: 10.1152/japplphysiol.00053.2012
Abstract: NAD(P)H oxidase-induced oxidative stress is at least in part involved with lowered exercise capacity and impaired mitochondrial function in high-fat diet (HFD)-induced diabetic mice. NAD(P)H oxidase can be activated by activation of the renin-angiotensin system. We investigated whether ANG II receptor blocker can improve exercise capacity in diabetic mice. C57BL/6J mice were fed a normal diet (ND) or HFD, and each group of mice was divided into two groups: treatment with or without olmesartan (OLM; 3 mg·kg−1·day−1 in the drinking water). The following groups of mice were studied: ND, ND+OLM, HFD, and HFD+OLM (n = 10 for each group). After 8 wk, HFD significantly increased body weight, plasma glucose, and insulin compared with ND, and OLM did not affect these parameters in either group. Exercise capacity, as determined by treadmill tests, was significantly reduced in HFD, and this reduction was ameliorated in HFD+OLM. ADP-dependent mitochondrial respiration was significantly decreased, and NAD(P)H oxidase activity and superoxide production by lucigenin chemiluminescence were significantly increased in skeletal muscle from HFD, which were attenuated by OLM. There were no such effects by OLM in ND. We concluded that OLM ameliorated the decrease in exercise capacity in diabetic mice via improvement in mitochondrial function and attenuation of oxidative stress in skeletal muscle. These data may have a clinical impact on exercise capacity in the medical treatment of diabetes mellitus.
Type: article
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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