Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom; Mustansiriyah University, College of Medicine, Department of Chemistry and Biochemistry, Baghdad, Iraq.
Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
J Diabetes Complications. 2019 Dec;33(12):107412. doi: 10.1016/j.jdiacomp.2019.107412. Epub 2019 Aug 1.
Skeletal muscle insulin resistance is a characteristic feature of type 2 diabetes. The aim of this study was to examine the effect of contraction on insulin action using electrical pulse stimulation (EPS) in cultured skeletal muscle cells from insulin resistant type 2 diabetic patients.
Skeletal muscle cell cultures were established from 6 insulin resistant type 2 diabetic subjects and age and BMI matched non-diabetic control subjects. Day 7 differentiated myotubes were treated with or without EPS for 16 h, after which glucose uptake and AS160 phosphorylation were measured in the presence or absence of insulin.
In control myotubes, EPS resulted in increased phosphorylation of AMPKThr (vs no EPS; p < 0.01), and this was associated with increased glucose uptake (p < 0.05). Insulin in the absence of EPS increased glucose uptake and AS160Thr phosphorylation, and both effects were significantly enhanced by prior EPS. In the absence of EPS, AMPK activation was significantly increased (p < 0.01) in the diabetic vs control myotubes. Despite a comparable degree of AMPK activation following EPS, the action of insulin on glucose uptake (p < 0.05) and AS160Thr phosphorylation (p < 0.001) was decreased in the diabetic vs control myotubes.
EPS mediated AMPK activation enhances the effect of insulin on glucose uptake and AS160Thr phosphorylation in control myotubes replicating key metabolic benefits of exercise on insulin action in man. Conversely, insulin mediated glucose uptake and AS160Thr phosphorylation remain significantly decreased in diabetic vs control myotubes despite a comparable degree of AMPK activation following EPS.
骨骼肌胰岛素抵抗是 2 型糖尿病的特征。本研究旨在通过电脉冲刺激（EPS）在胰岛素抵抗的 2 型糖尿病患者的培养骨骼肌细胞中检查收缩对胰岛素作用的影响。
从 6 名胰岛素抵抗的 2 型糖尿病患者和年龄及 BMI 匹配的非糖尿病对照者中建立骨骼肌细胞培养物。第 7 天分化的肌管接受或不接受 EPS 治疗 16 小时，然后在存在或不存在胰岛素的情况下测量葡萄糖摄取和 AS160 磷酸化。
在对照肌管中，EPS 导致 AMPKThr 磷酸化增加（与无 EPS 相比，p<0.01），这与葡萄糖摄取增加有关（p<0.05）。无 EPS 的胰岛素增加葡萄糖摄取和 AS160Thr 磷酸化，并且这两种作用均被先前的 EPS 显著增强。在无 EPS 的情况下，与对照肌管相比，糖尿病肌管中 AMPK 激活显著增加（p<0.01）。尽管 EPS 后 AMPK 的激活程度相当，但胰岛素对葡萄糖摄取（p<0.05）和 AS160Thr 磷酸化（p<0.001）的作用在糖尿病肌管中降低。
EPS 介导的 AMPK 激活增强了 EPS 在对照肌管中对胰岛素作用的葡萄糖摄取和 AS160Thr 磷酸化的作用，复制了运动对人类胰岛素作用的关键代谢益处。相反，尽管 EPS 后 AMPK 的激活程度相当，但胰岛素介导的葡萄糖摄取和 AS160Thr 磷酸化在糖尿病肌管中仍然显著降低。
