title: Angiotensin II receptor blocker improves the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.
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.
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Shingo
authors: S
authors: Takada
authors: Shintaro
authors: S
authors: Kinugawa
authors: Kagami
authors: K
authors: Hirabayashi
authors: Tadashi
authors: T
authors: Suga
authors: Takashi
authors: T
authors: Yokota
authors: Masashige
authors: M
authors: Takahashi
authors: Arata
authors: A
authors: Fukushima
authors: Tsuneaki
authors: T
authors: Homma
authors: Taisuke
authors: T
authors: Ono
authors: Mochamad A
authors: MA
authors: Sobirin
authors: Yoshihiro
authors: Y
authors: Masaki
authors: Wataru
authors: W
authors: Mizushima
authors: Tomoyasu
authors: T
authors: Kadoguchi
authors: Koichi
authors: K
authors: Okita
authors: Hiroyuki
authors: H
authors: Tsutsui
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D017079:Exercise Tolerance / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan