Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle

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-h-immobilized 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 immobilization-induced rapid development of insulin resistance in skeletal muscle.