Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
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DOI：
10.2337/diabetes.54.1.8
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发表时间：
2005-01-01
期刊：
影响因子：
7.7
通讯作者：
Kelley, DE
中科院分区：
文献类型：
--
作者：
Ritov, VB;Menshikova, EV;Kelley, DE
目前的研究提出了一个新的假说，即2型糖尿病骨骼肌线粒体功能障碍的亚细胞分布。股外侧肌通过经皮活检从11名2型糖尿病志愿者、12名年龄、性别和体重匹配的肥胖久坐非糖尿病志愿者和8名瘦志愿者中获得。采用差速离心和消化技术分离肌膜下和肌原纤维间线粒体组分。2型糖尿病和肥胖受试者的总体电子传递链活性相似，但2型糖尿病受试者的肌膜下线粒体电子传递链活性降低（0.017 +/- 0.003 vs. 0.034 +/-0.007单位/mU肌酸激酶[CK]，P = 0.01），与瘦受试者相比降低了七倍（P < 0.01）。2型糖尿病和肥胖受试者肌原纤维间线粒体的电子传递链活性相似，但与瘦受试者相比有所降低。通过透射电子显微镜证实肌膜下线粒体减少。虽然2型糖尿病和肥胖患者的mtDNA水平较低，但电子传递链活性的下降幅度较大，表明功能受损。由于肌膜下线粒体对信号转导和底物转运的潜在重要性，这种缺陷可能有助于2型糖尿病肌肉胰岛素抵抗的发病机制。
The current study addresses a novel hypothesis of subcellular distribution of mitochondrial dysfunction in skeletal muscle in type 2 diabetes. Vastus lateralis muscle was obtained by percutaneous biopsy from 11 volunteers with type 2 diabetes; 12 age-, sex-, and weight-matched obese sedentary nondiabetic volunteers; and 8 lean volunteers. Subsarcolemmal and intermyofibrillar mitochondrial fractions were isolated by differential centrifugation and digestion techniques. Overall electron transport chain activity was similar in type 2 diabetic and obese subjects, but subsarcolemmal mitochondria electron transport chain activity was reduced in type 2 diabetic subjects (0.017 +/- 0.003 vs. 0.034 +/-0.007 units/mU creatine kinase [CK], P = 0.01) and sevenfold reduced compared with lean subjects (P < 0.01). Electron transport chain activity in intermyofibrillar mitochondria was similar in type 2 diabetic and obese subjects, though reduced compared with lean subjects. A reduction in subsarcolemmal mitochondria was confirmed by transmission electron microscopy. Although mtDNA was lower in type 2 diabetic and obese subjects, the decrement in electron transport chain activity was proportionately greater, indicating functional impairment. Because of the potential importance of subsarcolemmal mitochondria for signal transduction and substrate transport, this deficit may contribute to the pathogenesis of muscle insulin resistance in type 2 diabetes.