School of P.E. and Sports Science, Beijing Normal University, Beijing, 100875, China.
Endocrine. 2015 Feb;48(1):152-63. doi: 10.1007/s12020-014-0233-y. Epub 2014 Mar 20.
Interleukin 15 (IL-15) has recently been proposed as a circulating myokine involved in glucose uptake and utilization in skeletal muscle. However, the role and mechanism of IL-15 in exercise improving insulin resistance (IR) is unclear. Here, we investigated the alteration in expression of IL-15 and IL-15 receptor α (IL-15Rα) in skeletal muscle during treadmill running in rats with IR induced by a high-fat diet (HFD) and elucidated the mechanism of the anti-IR effects of IL-15. At 20 weeks of HFD, rats showed severe IR, with increased levels of fasting blood sugar and plasma insulin, impaired glucose tolerance, and reduced glucose transport activity. IL-15 immunoreactivity and mRNA level in gastrocnemius muscle were decreased markedly as compared with controls. IL-15Rα protein and mRNA levels in both soleus and gastrocnemius muscle were significantly decreased, which might attenuate the signaling or secretion of IL-15 in muscle. Eight-week treadmill running completely ameliorated HFD-induced IR and reversed the downregulated level of IL-15 and IL-15Rα in skeletal muscle of HFD-fed rats. To investigate whether IL-15 exerts its anti-IR effects directly in muscle, we pre-incubated muscle strips with the endoplasmic reticulum stress (ERS) inducer dithiothreitol (DTT) or tunicamycin (Tm); IL-15 treatment markedly decreased the protein expression of the ERS markers 78-kDa glucose-regulated protein, 94-kDa glucose-regulated protein and C/EBP homologous protein and inhibited ERS induced by DTT or Tm. Therefore, treadmill running promoted skeletal IL-15 and IL-15Rα expression in HFD-induced IR in rats. The inhibitory effect of IL-15 on ERS may be involved in improved insulin sensitivity with exercise training.
白细胞介素 15(IL-15)最近被提出作为一种循环肌因子,参与骨骼肌中的葡萄糖摄取和利用。然而,IL-15 在运动改善胰岛素抵抗(IR)中的作用和机制尚不清楚。在这里,我们研究了高脂饮食(HFD)诱导的 IR 大鼠在跑步机跑步过程中骨骼肌中 IL-15 和 IL-15 受体 α(IL-15Rα)表达的变化,并阐明了 IL-15 抗 IR 作用的机制。在 HFD 的 20 周时,大鼠表现出严重的 IR,空腹血糖和血浆胰岛素水平升高,葡萄糖耐量受损,葡萄糖转运活性降低。与对照组相比,腓肠肌中的 IL-15 免疫反应性和 mRNA 水平明显降低。比目鱼肌和腓肠肌中的 IL-15Rα 蛋白和 mRNA 水平均显著降低,这可能减弱肌肉中 IL-15 的信号转导或分泌。八周的跑步机跑步完全改善了 HFD 诱导的 IR,并逆转了 HFD 喂养大鼠骨骼肌中下调的 IL-15 和 IL-15Rα 水平。为了研究 IL-15 是否直接在肌肉中发挥其抗 IR 作用,我们用内质网应激(ERS)诱导剂二硫苏糖醇(DTT)或衣霉素(Tm)预孵育肌肉条;IL-15 处理显著降低了 ERS 标志物 78-kDa 葡萄糖调节蛋白、94-kDa 葡萄糖调节蛋白和 C/EBP 同源蛋白的蛋白表达,并抑制了 DTT 或 Tm 诱导的 ERS。因此,跑步机跑步促进了 HFD 诱导的 IR 大鼠骨骼肌中 IL-15 和 IL-15Rα 的表达。IL-15 对 ERS 的抑制作用可能与运动训练改善胰岛素敏感性有关。