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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.
MedLine Citation:
PMID:  23329824     Owner:  NLM     Status:  Publisher    
Introduction: NAD(P)H oxidase-induced oxidative stress is at least in part involved with the lowered exercise capacity and impaired mitochondrial function in high fat diet (HFD)-induced diabetic mice. NAD(P)H oxidase can be activated by the activation of renin-angiotensin system. Objective: We investigated whether angiotensin II receptor blocker can improve exercise capacity in diabetic mice. Methods and Results: C57BL/6J mice were fed on normal diet (ND) or HFD, and each group of mice was divided into 2 groups of the treatment with or without olmesartan (OLM, 3 mg/kg/day in the drinking water). ND, ND+OLM, HFD, and HFD+OLM (n = 10 for each group) were studied. After 8 wk, HFD significantly increased body weight, plasma glucose, and insulin compared to ND, and OLM did not affect these parameters in either group. Exercise capacity 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 the skeletal muscle from HFD, which were attenuated by OLM. There were no such effects by OLM in ND. Conclusions: OLM ameliorated the decrease in exercise capacity in diabetic mice via the improvement in mitochondrial function and attenuation of oxidative stress in the skeletal muscle. These data may have a clinical impact on exercise capacity in the medical treatment of diabetes mellitus.
Shingo Takada; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Takashi Yokota; Masashige Takahashi; Arata Fukushima; Tsuneaki Homma; Taisuke Ono; Mochamad Ali Sobirin; Yoshihiro Masaki; Tomoyasu Kadoguchi; Koichi Okita; Hiroyuki Tsutsui
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  -     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Hokkaido University Graduate School of Medicine.
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