Kirwan J P, del Aguila L F, Hernandez J M, Williamson D L, O'Gorman D J, Lewis R, Krishnan R K
Departments of Reproductive Biology and Nutrition, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio 44109, USA.
J Appl Physiol (1985). 2000 Feb;88(2):797-803. doi: 10.1152/jappl.2000.88.2.797.
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 (VO(2 max)) of 56.1 +/- 2.5 ml. kg(-1). min(-1)] and eight healthy sedentary men and women (24 +/- 1 yr, 64.7 +/- 4.4 kg, VO(2 max) 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 (VO(2 max)) 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-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.
规律运动可增强胰岛素在骨骼肌中的作用。习惯性运动是否会影响人类骨骼肌中的胰岛素信号传导尚不清楚。磷脂酰肌醇3激酶（PI3激酶）的激活是胰岛素信号通路中的重要一步，似乎通过骨骼肌中GLUT - 4的转位来调节葡萄糖代谢。为了研究规律运动对PI3激酶激活的影响，对8名健康的运动训练者[24±1岁，71.8±2.0 kg，最大摄氧量（VO₂max）为56.1±2.5 ml·kg⁻¹·min⁻¹]和8名健康的久坐不动的男性和女性（24±1岁，64.7±4.4 kg，VO₂max为44.4±2.7 ml·kg⁻¹·min⁻¹）进行了2小时的高胰岛素血症（40 mU·m⁻²·min⁻¹）-正常血糖（5.0 mM）钳夹试验。使用[6, 6-(²)H]葡萄糖示踪剂来测量肝脏葡萄糖输出。在基础状态和高胰岛素血症2小时时，从股外侧肌获取肌肉活检样本，以测量与胰岛素受体底物-1（IRS-1）相关的PI3激酶激活情况。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置率（GDR）更高（P<0.05）（9.22±0.95 vs. 6.36±0.57 mg·kg去脂体重⁻¹·min⁻¹）。与久坐组相比，训练组中胰岛素刺激的PI3激酶激活也更高（P<0.004）（从基础值增加3.8±0.5倍 vs. 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激酶与肌肉形态之间无相关性。然而，GDR的增加与PI3激酶激活呈正相关（r = 0.60，P<0.02）。我们得出结论，规律运动可导致人类骨骼肌中胰岛素刺激的与IRS-1相关的PI3激酶激活增加，从而促进胰岛素介导的葡萄糖摄取增强。
