Increased proton leak and SOD2 expression in myotubes from obese non-diabetic subjects with a family history of type 2 diabetes
Increased proton leak and SOD2 expression in myotubes from obese non-diabetic subjects with a family history of type 2 diabetes
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DOI：
10.1016/j.bbadis.2013.05.008
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发表时间：
2013-10-01
影响因子：
6.2
通讯作者：
Harper, Mary-Ellen
中科院分区：
文献类型：
--
作者：
Aguer, Celine;Pasqua, Melissa;Harper, Mary-Ellen
肌肉胰岛素抵抗与氧化应激和线粒体功能下降有关。然而，肌肉胰岛素抵抗的确切原因尚不清楚。由于2型糖尿病（T2DM）患者的后代易发生胰岛素抵抗，因此他们是研究胰岛素抵抗早期发展的理想对象。通过使用来自有（FH+）或没有（FH-） T2DM家族史的肥胖非糖尿病受试者的原代肌肉细胞，我们旨在更好地了解线粒体功能、氧化应激和肌肉胰岛素抵抗之间的联系。胰岛素刺激的葡萄糖摄取和糖原合成在FH+肌管中正常。各组间静息耗氧量差异无统计学意义。而FH+肌管中质子漏量较高。这与FH+肌管中ATP含量降低和线粒体膜电位降低有关。令人惊讶的是，FH+肌管中mtDNA含量更高。氧化应激水平在FH+组和FH-组之间无显著差异。在高葡萄糖/胰岛素（25 mM/150 pM）分化时，FH+肌管中的活性氧含量较低，这可能是由于更高的氧化应激防御（SOD2表达和不耦合呼吸）。FH+肌管中抗氧化防御和mtDNA含量的增加提示存在代偿机制，这可能暂时阻止胰岛素抵抗的发展。(C) 2013 Elsevier B.V.版权所有
Muscle insulin resistance is linked to oxidative stress and decreased mitochondrial function. However, the exact cause of muscle insulin resistance is still unknown. Since offspring of patients with type 2 diabetes mellitus (T2DM) are susceptible to developing insulin resistance, they are ideal for studying the early development of insulin resistance. By using primary muscle cells derived from obese non-diabetic subjects with (FH+) or without (FH-) a family history of T2DM, we aimed to better understand the link between mitochondrial function, oxidative stress, and muscle insulin resistance. Insulin-stimulated glucose uptake and glycogen synthesis were normal in FH+ myotubes. Resting oxygen consumption rate was not different between groups. However, proton leak was higher in FH+ myotubes. This was associated with lower ATP content and decreased mitochondrial membrane potential in FH+ myotubes. Surprisingly, mtDNA content was higher in FH+ myotubes. Oxidative stress level was not different between FH+ and FH- groups. Reactive oxygen species content was lower in FH+ myotubes when differentiated in high glucose/insulin (25 mM/150 pM), which could be due to higher oxidative stress defenses (SOD2 expression and uncoupled respiration). The increased antioxidant defenses and mtDNA content in FH+ myotubes suggest the existence of compensatory mechanisms, which may provisionally prevent the development of insulin resistance. (C) 2013 Elsevier B.V. All rights reserved.