Sirtuin 1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle.
Sirtuin 1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle.
复制标题
小鼠骨骼肌收缩刺激的葡萄糖摄取不需要 Sirtuin 1。
DOI：
10.1152/japplphysiol.00065.2021
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Schenk,Simon
中科院分区：
文献类型：
--
作者：
Kang,JiH;Park,JiE;Dagoon,Jason;Masson,StewartWC;Merry,TroyL;Bremner,ShannonN;Dent,JessicaR;Schenk,Simon
虽然人们早就知道收缩强烈刺激骨骼肌葡萄糖摄取，但调节这种增加的分子步骤仍然不完全确定。Sir 2的哺乳动物直系同源物sirtuin 1（SIRT 1）是一种NAD+依赖性蛋白脱乙酰酶，被认为将与运动相关的能量通量扰动与随后的细胞适应联系起来。然而，其在收缩刺激的葡萄糖摄取中的作用尚未被描述。本研究的目的是确定SIRT 1对小鼠骨骼肌收缩刺激葡萄糖摄取的重要性。使用放射性2-脱氧葡萄糖摄取（2DOGU）的方法，我们测量了离体葡萄糖摄取在未刺激（休息）和电刺激（100 Hz收缩，每15秒10分钟;收缩）趾长伸肌（EDL）和比目鱼肌从1015周龄的男性和女性的肌肉特异性敲除SIRT 1脱乙酰酶活性和野生型同窝小鼠。虽然基因型之间的疲劳率没有差异，但在收缩过程中，骨骼肌的力量下降了。在EDL和比目鱼肌中，SIRT 1脱乙酰酶活性的丧失并不影响收缩诱导的葡萄糖摄取增加。有趣的是，无论肌肉类型如何，雌性小鼠的收缩刺激2DOGU的绝对速率都比雄性小鼠高1.4倍。总之，我们的研究结果表明，SIRT 1是不需要收缩刺激的小鼠骨骼肌中的葡萄糖摄取。此外，据我们所知，这是第一次证明基于性别的差异，在收缩刺激的葡萄糖摄取在小鼠骨骼肌。新&值得注意的是，我们证明，葡萄糖摄取在响应离体收缩是不受影响的损失sirtuin 1（SIRT 1）脱乙酰酶功能的肌肉，无论性别或肌肉类型。然而，有趣的是，类似于胰岛素刺激的葡萄糖摄取的研究，我们表明，收缩刺激的葡萄糖摄取是稳健的女性相比，男性骨骼肌。据我们所知，这是第一次证明骨骼肌收缩刺激葡萄糖摄取的性别差异。
While it has long been known that contraction robustly stimulates skeletal muscle glucose uptake, the molecular steps regulating this increase remain incompletely defined. The mammalian ortholog of Sir2, sirtuin 1 (SIRT1), is an NAD+-dependent protein deacetylase that is thought to link perturbations in energy flux associated with exercise to subsequent cellular adaptations. Nevertheless, its role in contraction-stimulated glucose uptake has not been described. The objective of this study was to determine the importance of SIRT1 to contraction-stimulated glucose uptake in mouse skeletal muscle. Using a radioactive 2-deoxyglucose uptake (2DOGU) approach, we measured ex vivo glucose uptake in unstimulated (rested) and electrically stimulated (100 Hz contraction every 15 s for 10 min; contracted) extensor digitorum longus (EDL) and soleus from ∼15-wk-old male and female mice with muscle-specific knockout of SIRT1 deacetylase activity and their wild-type littermates. Skeletal muscle force decreased over the contraction protocol, although there were no differences in the rate of fatigue between genotypes. In EDL and soleus, loss of SIRT1 deacetylase activity did not affect contraction-induced increase in glucose uptake in either sex. Interestingly, the absolute rate of contraction-stimulated 2DOGU was ∼1.4-fold higher in female compared with male mice, regardless of muscle type. Taken together, our findings demonstrate that SIRT1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle. Moreover, to our knowledge, this is the first demonstration of sex-based differences in contraction-stimulated glucose uptake in mouse skeletal muscle.NEW & NOTEWORTHYHere, we demonstrate that glucose uptake in response to ex vivo contractions is not affected by the loss of sirtuin 1 (SIRT1) deacetylase function in muscle, regardless of sex or muscle type. Interestingly, however, similar to studies on insulin-stimulated glucose uptake, we demonstrate that contraction-stimulated glucose uptake is robustly higher in female compared with the male skeletal muscle. To our knowledge, this is the first demonstration of sex-based differences in contraction-stimulated glucose uptake in skeletal muscle.