The mechanism of exercise-induced increase in muscle insulin sensitivity

2型糖尿病和肥胖症以骨骼肌胰岛素抵抗为特征。运动可以提高骨骼肌的胰岛素敏感性。然而，目前尚不清楚单次运动如何提高随后的胰岛素敏感性。最近，有报道称巨噬细胞至少部分地调节几种胰岛素靶器官的胰岛素敏感性。因此，我们假设巨噬细胞参与了运动诱导的骨骼肌胰岛素敏感性增强的机制。为了验证这一假设，我们给C57BL6J小鼠注射了巨噬细胞抑制剂生理盐水（SAL）或氯钠脂质体（CL）。然后，让老鼠在跑步机上跑一圈。运动后24小时，我们测量了体外胰岛素刺激下骨骼肌2-脱氧葡萄糖（DG）的摄取。我们观察到，在SAL组中，单次运动增强了巨噬细胞的积累和胰岛素刺激的跖肌2-DG摄取。然而，CL治疗完全消除了这些变化。我们还观察到Akt、AS160和AMPK的磷酸化状态未因CL处理而改变。根据这些结果，我们得出结论，巨噬细胞参与了运动诱导的骨骼肌胰岛素敏感性增强的机制，独立于Akt和AMPK磷酸化状态。

Type 2 diabetes and obesity are characterized by insulin resistance in skeletal muscle. It has been well demonstrated that exercise increase insulin sensitivity in skeletal muscle. However, it remains still unclear how a single bout exercise enhance subsequent insulin sensitivity. Recently, it has been reported that macrophages, at least partly, regulate insulin sensitivity in several insulin target organs. We, therefore, hypothesized that macrophages are involved in the mechanisms of exercise-induced enhancement of insulin sensitivity in skeletal muscle. To test this hypothesis, we injected saline (SAL) or clodronate liposome (CL), a macrophage suppressor, to C57BL6J mice. Then, mice were subjected to a single bout of treadmill running. Twenty-four hour after exercise, we measured ex-vivo insulin-stimulated 2-deoxy glucose (DG) uptake in skeletal muscle. We observed that a single bout exercise enhanced macrophage accumulation and insulin-stimulated 2-DG uptake in plantaris muscle in SAL group. However, CL treatment completely abolished these changes. We also observed that phosphorylation state of Akt, AS160 and AMPK were not changed by CL treatment. From these results, we conclude that macrophages are involved in the mechanisms of exercise-induced enhancement of insulin sensitivity in skeletal muscle, independent of Akt and AMPK phosphorylation states.