Electrical pulse stimulation induces differential responses in insulin action in myotubes from severely obese individuals.
Electrical pulse stimulation induces differential responses in insulin action in myotubes from severely obese individuals.
复制标题
电脉冲刺激会引起严重肥胖个体肌管中胰岛素作用的差异反应。
DOI：
10.1113/jp276990
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Houmard,JosephA
中科院分区：
文献类型：
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作者：
Park,Sanghee;Turner,KristenD;Zheng,Donghai;Brault,JeffreyJ;Zou,Kai;Chaves,AlecB;Nielsen,ThomasS;Tanner,CharlesJ;Treebak,JonasT;Houmard,JosephA
锻炼/运动训练可以通过骨骼肌的适应来增强胰岛素敏感性，骨骼肌是胰岛素介导的葡萄糖处理的主要部位；然而，在人类中，改善的幅度可能有很大的不同。本研究的目的是确定肥胖是否影响运动反应的幅度，与改善人类骨骼肌的胰岛素敏感性有关。24小时)的原始人体骨骼肌管改善了组织中胰岛素的作用，但对EPS的反应因肥胖而变得迟钝。EPS改善了精瘦但不严重肥胖的受试者肌管中的胰岛素信号转导，并增加了AMP的积累和AMPK-172的磷酸化，但在严重肥胖者的肌管中的作用程度较小。这些数据表明，严重肥胖者的肌管增强胰岛素作用，并通过收缩刺激运动反应分子，但方式和幅度与瘦受试者不同。运动/肌肉收缩可以增强全身胰岛素的敏感性；然而，在人类中，改善的范围可能会有很大不同。为了确定肥胖是否会影响运动反应的幅度，这项研究比较了电脉冲刺激诱导的收缩活动对瘦和严重肥胖(体重指数为40≥/m2)女性的初级肌管的影响。在肌肉收缩之前，严重肥胖者肌管中的胰岛素作用受到抑制，表现为胰岛素刺激的糖原合成减少、葡萄糖氧化、葡萄糖摄取、胰岛素信号转导(IRS1、Akt、TbC1D4)和胰岛素刺激的GLUT4移位。EPS(24小时)使瘦肥胖者和重度肥胖者肌管上AMP、IMP、AMPK Thr172磷酸化、Pgc1α含量和胰岛素作用均增加。然而，尽管胰岛素作用指数正常化到瘦身对照(非EPS)状态下的水平，但肥胖使EPS的反应变得迟钝。EPS可促进瘦肉型但非重度肥胖者肌管胰岛素信号转导，EPS可增加AMP积聚和AMPK Thr172磷酸化，但对重度肥胖者肌管内AMP积聚和AMPK Thr172磷酸化的影响较小。这些数据表明，严重肥胖的人的肌管增强了胰岛素的作用，并通过收缩刺激运动反应分子，但方式和幅度与瘦人不同。
Key pointsExercise/exercise training can enhance insulin sensitivity through adaptations in skeletal muscle, the primary site of insulin‐mediated glucose disposal; however, in humans the range of improvement can vary substantially.The purpose of this study was to determine if obesity influences the magnitude of the exercise response in relation to improving insulin sensitivity in human skeletal muscle.Electrical pulse stimulation (EPS; 24 h) of primary human skeletal muscle myotubes improved insulin action in tissue from both lean and severely obese individuals, but responses to EPS were blunted with obesity.EPS improved insulin signal transduction in myotubes from lean but not severely obese subjects and increased AMP accumulation and AMPK Thr172phosphorylation, but to a lesser degree in myotubes from the severely obese.These data reveal that myotubes of severely obese individuals enhance insulin action and stimulate exercise‐responsive molecules with contraction, but in a manner and magnitude that differs from lean subjects.AbstractExercise/muscle contraction can enhance whole‐body insulin sensitivity; however, in humans the range of improvements can vary substantially. In order, to determine if obesity influences the magnitude of the exercise response, this study compared the effects of electrical pulse stimulation (EPS)‐induced contractile activity upon primary myotubes derived from lean and severely obese (BMI ≥ 40 kg/m2) women. Prior to muscle contraction, insulin action was compromised in myotubes from the severely obese as was evident from reduced insulin‐stimulated glycogen synthesis, glucose oxidation, glucose uptake, insulin signal transduction (IRS1, Akt, TBC1D4), and insulin‐stimulated GLUT4 translocation. EPS (24 h) increased AMP, IMP, AMPK Thr172phosphorylation, PGC1α content, and insulin action in myotubes of both the lean and severely obese subjects. However, despite normalizing indices of insulin action to levels seen in the lean control (non‐EPS) condition, responses to EPS were blunted with obesity. EPS improved insulin signal transduction in myotubes from lean but not severely obese subjects and EPS increased AMP accumulation and AMPK Thr172phosphorylation, but to a lesser degree in myotubes from the severely obese. These data reveal that myotubes of severely obese individuals enhance insulin action and stimulate exercise‐responsive molecules with contraction, but in a manner and magnitude that differs from lean subjects.