The mechanism of exercise-induced increase in muscle insulin sensitivity

2型糖尿病和肥胖症的特征在于骨骼肌中的胰岛素抵抗。研究表明，运动可以增加骨骼肌对胰岛素的敏感性。然而，目前还不清楚一次运动如何提高随后的胰岛素敏感性。最近，据报道，巨噬细胞，至少部分，调节胰岛素敏感性在几个胰岛素靶器官。因此，我们推测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，我们将生理盐水（SAL）或氯膦酸盐脂质体（CL）（巨噬细胞抑制剂）注射到C57 BL 6 J小鼠中。然后，小鼠进行一次跑步机跑步。运动后24小时，我们测量了离体胰岛素刺激的骨骼肌2-脱氧葡萄糖（DG）摄取。我们观察到，一次运动可以增强SAL组巨噬细胞的聚集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。CL对Akt、AS 160和AMPK的磷酸化状态无明显影响。从这些结果中，我们得出结论，巨噬细胞参与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.