Table_4_Transcriptomic Responses of Skeletal Muscle to Acute Exercise in Diabetic Goto-Kakizaki Rats.XLSX

Physical activity exerts positive effects on glycemic control in type 2 diabetes (T2D), which is mediated in part by extensive metabolic and molecular remodeling of skeletal muscle in response to exercise, while many regulators of skeletal muscle remain unclear. In the present study, we investigated the effects of acute exercise on skeletal muscle transcriptomic responses in the Goto-Kakizaki (GK) rats which can spontaneously develop T2D. The transcriptomes of skeletal muscle from both 8-week-old GK and Wistar rats that underwent a single exercise session (60 min running using an animal treadmill at 15 m/min) or remained sedentary were analyzed by next-generation RNA sequencing. We identified 819 differentially expressed genes in the sedentary GK rats compared with those of the sedentary Wistar rats. After a single bout of running, we found 291 and 598 genes that were differentially expressed in the exercise GK and exercise Wistar rats when compared with the corresponding sedentary rats. By integrating our data and previous studies including RNA or protein expression patterns and transgenic experiments, the downregulated expression of Fasn and upregulated expression of Tbc1d1, Hk2, Lpin1, Ppargc1a, Sorbs1, and Hmox1 might enhance glucose uptake or improve insulin sensitivity to ameliorate hyperglycemia in the exercise GK rats. Our results provide mechanistic insight into the beneficial effects of exercise on hyperglycemia and insulin action in skeletal muscle of diabetic GK rats.

体力活动对2型糖尿病（T2D）的血糖控制具有积极影响，部分是通过骨骼肌对运动产生的广泛代谢和分子重构来介导的，而许多调节骨骼肌的因素仍不明确。在本研究中，我们探讨了急性运动对Goto-Kakizaki（GK）大鼠骨骼肌转录组反应的影响，GK大鼠能够自发地发展成T2D。通过对8周大的GK和Wistar大鼠在单次运动训练（使用动物跑步机进行60分钟，速度为15米/分钟）后或保持久坐状态下骨骼肌的转录组进行了下一代RNA测序分析。我们发现在久坐的GK大鼠中，与久坐的Wistar大鼠相比，存在819个差异表达基因。在单次跑步训练后，我们发现与相应的久坐大鼠相比，运动后的GK和Wistar大鼠中有291个和598个基因表达存在差异。通过整合我们的数据和包括RNA或蛋白质表达模式以及转基因实验在内的先前研究，我们发现Fasn表达下调，而Tbc1d1、Hk2、Lpin1、Ppargc1a、Sorbs1和Hmox1表达上调，可能增强葡萄糖摄取或改善胰岛素敏感性，从而改善运动后GK大鼠的高血糖症状。我们的研究结果为运动对糖尿病GK大鼠骨骼肌中高血糖和胰岛素作用的有益影响提供了机制上的见解。