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

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 recept...

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Bibliographic Details
Published in:Journal of applied physiology (1985) 2013-04, Vol.114 (7), p.844-857
Main Authors: Takada, Shingo, Kinugawa, Shintaro, Hirabayashi, Kagami, Suga, Tadashi, Yokota, Takashi, Takahashi, Masashige, Fukushima, Arata, Homma, Tsuneaki, Ono, Taisuke, Sobirin, Mochamad A, Masaki, Yoshihiro, Mizushima, Wataru, Kadoguchi, Tomoyasu, Okita, Koichi, Tsutsui, Hiroyuki
Format: Article
Language:English
Subjects:
Angiotensin Receptor Antagonists - administration & dosage
Animals
Diabetes
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - physiopathology
Exercise Tolerance - drug effects
Imidazoles - administration & dosage
Male
Mice
Mice, Inbred C57BL
Mitochondria
Mitochondria, Muscle - drug effects
Muscle, Skeletal - drug effects
Muscle, Skeletal - physiopathology
Musculoskeletal system
Oxidative stress
Oxidative Stress - drug effects
Peptides
Physiology
Rodents
Tetrazoles - administration & dosage
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Summary: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.
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.00053.2012