High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D
High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D
复制标题
高不完全骨骼肌脂肪酸氧化解释了控制不佳的T2D患者的低肌肉胰岛素敏感性
DOI：
10.1210/jc.2017-01727
复制
发表时间：
2018-03-01
影响因子：
5.8
通讯作者：
Dohm, G. Lynis
中科院分区：
文献类型：
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作者：
Gavin, Timothy P.;Ernst, Jacob M.;Dohm, G. Lynis
背景：近50%的2型糖尿病（T2D）患者控制不良[糖化血红蛋白(HbA1c) >= 7%]；然而，导致血糖控制逐渐恶化的机制尚不清楚。较低的骨骼肌线粒体呼吸能力与低胰岛素敏感性和T2D的发展有关。目的：研究控制良好的T2D （WCD）和控制不佳的T2D （PCD）之间骨骼肌胰岛素敏感性（SI）是否存在差异，以及这种差异是否与线粒体呼吸功能差异有关。设计：测定股外侧肌线粒体呼吸、线粒体含量、线粒体酶活性和脂肪酸氧化（FAO）。SI和对葡萄糖的急性反应（AIRg）是通过MINMOD分析从改良的、频繁采样的静脉葡萄糖耐量试验中获得的葡萄糖和胰岛素计算出来的。结果：PCD患者SI、AIRg低于WCD患者。PCD患者的肌肉不完全FAO高于WCD患者，且肌肉不完全FAO与较低的SI和较高的HbA1c相关。羟基酰基辅酶A脱氢酶在PCD中的表达和活性高于WCD。WCD与PCD在最大线粒体呼吸量和含量上无显著差异。结论：目前的结果表明，在控制不良的T2D中，骨骼肌不完全FAO的增加是由于β氧化升高，并与肌肉S恶化有关。
Context: Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) >= 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D.Objective: We investigated if skeletal muscle insulin sensitivity (SI) was different between wellcontrolled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function.Design: Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test.Results: SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacylcoenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD.Conclusion: The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated beta oxidation and is associated with worsening muscle S,.