Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle
Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle
复制标题
DOI：
10.1152/jappl.2000.88.2.797
复制
发表时间：
2000-02-01
影响因子：
3.3
通讯作者：
Krishnan, RK
中科院分区：
文献类型：
--
作者：
Kirwan, JP;Del Aguila, LF;Krishnan, RK
定期锻炼可以增强骨骼肌中的胰岛素作用。人类骨骼肌中的胰岛素信号是否受到习惯性运动的影响尚不清楚。磷脂酰肌醇 3-激酶 (PI3-激酶) 激活是胰岛素信号通路中的重要步骤，似乎通过骨骼肌中的 GLUT-4 易位调节葡萄糖代谢。为了检查定期运动对 PI3-激酶激活的影响，对 8 名健康人进行了 2 小时高胰岛素 (40 mU . m(-2) min(-1))-正常血糖 (5.0 mM) 钳夹运动训练 [24 +/- 1 年，71.8 +/- 2.0 kg，最大 O-2 摄取量 (VO2max) 58.1 +/- 2.5 ml。千克（-1）。 min(-1)] 和八名健康久坐的男性和女性（24 +/- 1 年，64.7 +/- 4.4 kg，最大摄氧量 44.4 +/- 2.7 ml . kg(-1) . min(-1)）。 [6,6(-2)H]葡萄糖示踪剂用于测量肝葡萄糖输出。在基础和高胰岛素血症 2 小时时从股外侧肌进行肌肉活检，以测量胰岛素受体底物 1 (IRS-1) 相关的 PI3 激酶激活。两组在高胰岛素血症期间的胰岛素浓度相似（训练组和久坐组分别为 293 +/- 22 和 311 +/- 22 pM）。与久坐对照组相比，运动训练组的胰岛素介导的葡萄糖处理率 (GDR) 更高 (P < 0.05)（9.22 +/- 0.95 vs. 6.36 +/- 0.57 mg·kg 去脂质量(-1)·min(-1)）。与久坐组相比，训练组中胰岛素刺激的 PI3 激酶激活也更大 (P < 0.004)（较基础值增加 3.8 +/- 0.5 倍与 1.8 +/- 0.2 倍）。耐力能力（VO2max）与 PI3 激酶激活呈正相关（r = 0.53，P < 0.04）。 PI3激酶和肌肉形态之间没有相关性。然而，GDR 的增加与 PI3 激酶激活呈正相关（r = 0.60，P < 0.02）。我们得出的结论是，定期运动会导致人体骨骼肌中胰岛素刺激的 IRS-1 相关 PI3 激酶活化程度更高，从而促进胰岛素介导的葡萄糖摄取增强。
Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle, To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU . m(-2) min(-1))-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 +/- 1 yr, 71.8 +/- 2.0 kg, maximal O-2 uptake (VO2max) of 58.1 +/- 2.5 ml . kg(-1) . min(-1)] and eight healthy sedentary men and women (24 +/- 1 yr, 64.7 +/- 4.4 kg, VO2max of 44.4 +/- 2.7 ml . kg(-1) . min(-1)). A [6,6(-2)H] glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 +/- 22 and 311 +/- 22 pM for trained and sedentary, respectively). Insulin-mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 +/- 0.95 vs. 6.36 +/- 0.57 mg . kg fat-free mass(-1) . min(-1)). Insulin-stimulated PI3-kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 +/- 0.5- vs. 1.8 +/- 0.2-fold increase from basal). Endurance capacity (VO2max) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-l-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.