Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes
Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes
复制标题
DOI：
10.2337/diabetes.51.10.2944
复制
发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Ritov, VB
中科院分区：
文献类型：
--
作者：
Kelley, DE;He, J;Ritov, VB
骨骼肌强烈依赖氧化磷酸化来产生能量。由于2型糖尿病和肥胖症患者骨骼肌的胰岛素抵抗导致碳水化合物和脂质燃料的氧化失调，因此本研究旨在检查线粒体功能扰动的潜在贡献。在空腹条件下，通过经皮活检从瘦（n = 10）和肥胖（n = 10）非糖尿病志愿者和2型糖尿病志愿者（n = 10）中获得股外侧肌。鱼藤酮敏感的NADH：O-2氧化还原酶的活性，反映了呼吸链的整体活性，通过一种新的方法在线粒体组分中进行测量，该方法基于通过丙甲霉素（一种通道形成抗生素）为NADH提供完整线粒体的通路。肌酸激酶和柠檬酸合酶活性分别作为肌细胞和线粒体含量的标志物进行测量。鱼藤酮敏感的NADH：O-2氧化还原酶的活性被标准化为肌酸激酶活性，柠檬酸合酶活性也是如此。NADH：O-2氧化还原酶活性在2型糖尿病受试者中最低，在瘦志愿者中最高（瘦志愿者0.95 +/- 0.17，肥胖志愿者0.76 +/- 0.30，2型糖尿病志愿者0.56 +/- 0.14单位/mU肌酸激酶; P < 0.005）。此外，2型糖尿病患者的柠檬酸合酶活性降低（瘦3.10 +/- 0.74，肥胖3.24 +/- 0.82，2型糖尿病2.48 +/- 0.47单位/mU肌酸激酶; P < 0.005）。电镜观察发现，2型糖尿病和肥胖者骨骼肌线粒体明显小于瘦志愿者（P < 0.01）。我们的结论是，2型糖尿病患者骨骼肌线粒体的生物能量能力受损，肥胖患者也存在一定程度的损伤。
Skeletal muscle is strongly dependent on oxidative phosphorylation for energy production. Because the insulin resistance of skeletal muscle in type 2 diabetes and obesity entails dysregulation of the oxidation of both carbohydrate and lipid fuels, the current study was undertaken to examine the potential contribution of perturbation of mitochondrial function. Vastus lateralis muscle was obtained by percutaneous biopsy during fasting conditions from lean (n = 10) and obese (n = 10) nondiabetic volunteers and from volunteers with type 2 diabetes (n = 10). The activity of rotenone-sensitive NADH:O-2 oxidoreductase, reflecting the overall activity of the respiratory chain, was measured in a mitochondrial fraction by a novel method based on providing access for NADH to intact mitochondria via alamethicin, a channel-forming antibiotic. Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively. Activity of rotenone-sensitive NADH:O-2 oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity. NADH:O-2 oxidoreductase activity was lowest in type 2 diabetic subjects and highest in the lean volunteers (lean 0.95 +/- 0.17, obese 0.76 +/- 0.30, type 2 diabetes 0.56 +/- 0.14 units/mU creatine kinase; P < 0.005). Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005). As measured by electron microscopy, skeletal muscle mitochondria were smaller in type 2 diabetic and obese subjects than in muscle from lean volunteers (P < 0.01). We conclude that there is an impaired bioenergetic capacity of skeletal muscle mitochondria in type 2 diabetes, with some impairment also present in obesity.