Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle
Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle
复制标题
DOI：
10.1152/japplphysiol.00951.2017
复制
发表时间：
2018-08-01
影响因子：
3.3
通讯作者：
Kawanaka, Kentaro
中科院分区：
文献类型：
--
作者：
Kawamoto, Emi;Tamakoshi, Keigo;Kawanaka, Kentaro
急性短期废用诱导啮齿动物骨骼肌葡萄糖摄取的胰岛素抵抗的发展。由于硫氧还蛋白相互作用蛋白（TXNIP）参与了胰岛素信号传导和葡萄糖摄取的下调，我们研究了肌肉废用通过增加TXNIP mRNA和蛋白表达快速诱导胰岛素抵抗的可能性。雄性Wistar大鼠单侧后肢石膏固定6小时。在这一时期结束时，比目鱼肌从固定和对侧非固定后肢切除和检查。6小时的制动导致TXNIP mRNA和蛋白表达的增加，以及胰岛素刺激的2-脱氧葡萄糖摄取在大鼠比目鱼肌减少。此外，在石膏模型移除后6小时安乐死的大鼠中，固定肌肉中TXNIP蛋白表达和胰岛素刺激的葡萄糖摄取均恢复到正常水平。各种干预措施（用转录抑制剂放线菌素D或AMP依赖性蛋白激酶激活剂5-氨基咪唑-4-甲酰胺核苷酸预处理）也抑制了TXNIP蛋白在6-himmobilized肌肉中表达的增加，并部分预防了葡萄糖摄取的胰岛素抵抗。这些结果表明，在固定大鼠比目鱼肌TXNIP蛋白的表达增加的可能性，与快速诱导胰岛素抵抗葡萄糖摄取在该tissue.NEW &值得注意的细胞机制，其中废用快速诱导肌肉胰岛素抵抗葡萄糖摄取仍有待确定。使用大鼠后肢制动模型，我们的研究结果表明，硫氧还蛋白相互作用蛋白的转录上调与immobilationinduced快速发展的胰岛素抵抗骨骼肌的可能性。
Acute short duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Because thioredoxin-interacting protein) (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-h hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral nonimmobilized hindlimbs were excised and examined. The 6-h immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats euthanized 6 h after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions )(pretreatment with transcription inhibitor actinomycin D or AMP-dependent protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleotide) also suppressed the increase in TXNIP protein expression in 6-himmobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue.NEW & NOTEWORTHY The cellular mechanism by which disuse rapidly induces muscle insulin resistance for glucose uptake remains to be identified. Using a rat hindlimb immobilization model, our findings suggest the possibility that transcriptional upregulation of thioredoxin-interacting protein is associated with the immobilizationinduced rapid development of insulin resistance in skeletal muscle.