Angiotensin II Receptor Blocker Improves the Lowered Exercise Capacity and Impaired Mitochondrial Function of the Skeletal Muscle in Type 2 Diabetic Mice.
Angiotensin II Receptor Blocker Improves the Lowered Exercise Capacity and Impaired Mitochondrial Function of the Skeletal Muscle in Type 2 Diabetic Mice.
复制标题
血管紧张素 II 受体阻滞剂可改善 2 型糖尿病小鼠运动能力下降和骨骼肌线粒体功能受损。
DOI：
10.1152/japplphysiol.00053.2012
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发表时间：
2013
影响因子：
3.3
通讯作者：
Tsutsui H.
中科院分区：
文献类型：
--
作者：
Takada S;Kinugawa S;Hirabayashi K;Suga T;Yokota T;Takahashi M;Fukushima A;Homma T;Ono T;Sobirin MA;Masaki Y;Mizushima W;Kadoguchi T;Okita K;Tsutsui H.
NAD（P）H氧化酶诱导的氧化应激至少部分与高脂饮食（HFD）诱导的糖尿病小鼠运动能力降低和线粒体功能受损有关。NAD（P）H氧化酶可通过激活肾素-血管紧张素系统而被激活。我们研究了血管紧张素Ⅱ受体阻断剂是否能改善糖尿病小鼠的运动能力。C57 BL/6 J小鼠饲喂正常饮食（ND）或HFD，每组小鼠分为两组：给予或不给予奥美沙坦（OLM; 3 mg·kg-1·day-1，在饮用水中）。研究了以下小鼠组：ND、ND+OLM、HFD和HFD+OLM（每组n= 10）。8周后，与ND相比，HFD显著增加体重、血糖和胰岛素，而OLM对两组的这些参数均无影响。运动能力，由平板试验确定，HFD组显著降低，HFD+OLM组改善了这种降低。OLM可抑制HFD引起的骨骼肌ADP依赖性线粒体呼吸作用，并使NAD（P）H氧化酶活性和光泽精化学发光法测定的超氧化物生成量显著增加。OLM对ND无明显影响。我们的结论是，OLM通过改善线粒体功能和减轻骨骼肌中的氧化应激来改善糖尿病小鼠运动能力的下降。这些数据可能对糖尿病药物治疗中的运动能力产生临床影响。
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−1in 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.