Swim training sensitizes myocardial response to insulin: role of Akt-dependent eNOS activation.
Swim training sensitizes myocardial response to insulin: role of Akt-dependent eNOS activation.
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DOI：
10.1016/j.cardiores.2007.04.015
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发表时间：
2007-07
影响因子：
10.8
通讯作者：
Quanjiang Zhang;Qiu-xia Li;Hai-Feng Zhang;Kun-ru Zhang;Wen-yi Guo;Haichang Wang;Zhuan Zhou;
中科院分区：
文献类型：
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作者：
Quanjiang Zhang;Qiu-xia Li;Hai-Feng Zhang;Kun-ru Zhang;Wen-yi Guo;Haichang Wang;Zhuan Zhou;
目的体育活动对心脏功能有益是众所周知的。自主神经活动的改善被认为是这种有益效果的主要原因。然而，心肌对运动的内在反应背后的确切机制尚不清楚。本研究旨在研究游泳训练对心肌胰岛素反应的影响，特别关注内源性内皮型一氧化氮合酶(eNOS) -一氧化氮（NO）级联。方法对成年雄性SD大鼠进行为期10周的自由负荷游泳训练（3 h/d， 5 d /周）。评估心肌细胞和离体灌注心脏水平对胰岛素的收缩反应、心肌葡萄糖摄取和胰岛素受体后信号级联。结果游泳训练分别增强心肌细胞和离体灌注心脏对胰岛素的收缩反应。心脏反应的改善伴随着胰岛素刺激的葡萄糖摄取、GLUT4易位和Akt和eNOS表达的上调（p<0.01）。胰岛素治疗导致eNOS磷酸化增加3.6倍和2.2倍（p<0.01），运动组和久坐组Akt磷酸化分别增加3.0倍和1.9倍（p<0.01）。此外，运动显著促进胰岛素诱导的心肌NO生成（与久坐相比p<0.01）。此外，用磷脂酰肌醇-3激酶（PI-3K）抑制剂LY294002或NOS抑制剂l- name预处理，均可消除运动诱导的心肌对胰岛素收缩反应的增敏、胰岛素诱导的NO生成以及Akt和eNOS的磷酸化。结论：游泳训练可通过上调Akt-和eNOS信号级联通路，提高胰岛素对心肌收缩反应的敏感性。
ObjectivesPhysical activity has been well known to benefit heart function. The improved autonomic nervous activity is considered to be mainly responsible for this beneficial effect. However, the precise mechanism behind the intrinsic myocardial responsiveness to exercise is still unclear. This study was designed to examine the effect of swim training on myocardial response to insulin with a special focus on the endogenous endothelial nitric oxide synthase (eNOS)–nitric oxide (NO) cascade.MethodsAdult male Sprague–Dawley (SD) rats were subjected to a 10-week free-loading swim training (3 h/day, 5 days/week). Contractile response to insulin at the levels of cardiomyocytes and isolated perfused heart, myocardial glucose uptake and post-insulin receptor signaling cascades were evaluated.ResultsSwim training enhanced cardiac contractile response to insulin in cardiomyocytes and isolated perfused heart, respectively. The improved cardiac response was accompanied by facilitated insulin-stimulated glucose uptake, GLUT4 translocation and upregulation of Akt and eNOS expression (p<0.01). Treatment with insulin resulted in a 3.6- and 2.2-fold increase of eNOS phosphorylation (p<0.01), as well as a 3.0- and 1.9-fold increase of Akt phosphorylation in exercise and sedentary groups, respectively (p<0.01). In addition, exercise significantly facilitated insulin-induced myocardial NO production (p<0.01 vs. sedentary). Moreover, pretreatment with either LY294002, a phosphatidylinositol-3 kinase (PI-3K) inhibitor orl-NAME, a NOS inhibitor, abolished the exercise-induced sensitization of myocardial contractile response to insulin, insulin-induced NO production and phosphorylation of Akt and eNOS.ConclusionThese results demonstrate that swim training is capable of sensitizing myocardial contractile response to insulin via upregulation of Akt- and eNOS signaling cascades.