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The induction of insulin resistance in skeletal muscle is a key phenomenon to develop diabetes. However, the mechanisms linking IH stress and insulin resistance remain elusive. We exposed human RD and mouse C2C12 muscle cells to normoxia or IH and measured their mRNA levels by real\u2010time RT\u2010PCR. We found that IH significantly increased the mRNA and protein levels of muscle\u2010derived insulin resistance\u2010factors (myokines) such as IL\u20108, osteonectin (ON), and myonectin (MN) in muscle cells. We further analysed the IH\u2010induced expression mechanisms of <jats:italic>IL\u20108<\/jats:italic>, <jats:italic>ON<\/jats:italic>, and <jats:italic>MN<\/jats:italic> genes in muscle cells. Deletion analyses of the human myokine promoter(s) revealed that the regions \u2212152 to \u2212151 in <jats:italic>IL\u20108<\/jats:italic>, \u2212105 to \u221299 in <jats:italic>ON<\/jats:italic>, and\u2009\u2212\u20093741 to \u22123738 in <jats:italic>MN<\/jats:italic> promoters were responsible for the activation by IH in RD cells. The promoters contain consensus transcription factor binding sequences for OCT1 in <jats:italic>IL\u20108<\/jats:italic> and <jats:italic>MN<\/jats:italic> promoters, and for NRF2 in <jats:italic>ON<\/jats:italic> promoter, respectively. The introduction of siRNA for OCT1 abolished the IH\u2010induced expression(s) of <jats:italic>IL\u20108<\/jats:italic> and <jats:italic>MN<\/jats:italic> and siRNA for NRF2 abolished the IH\u2010induced expression of <jats:italic>ON<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/jcmm.17618","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T10:19:42Z","timestamp":1669976382000},"page":"6019-6031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Upregulation of <scp>IL<\/scp>\u20108, osteonectin, and myonectin <scp>mRNAs<\/scp> by intermittent hypoxia via <scp>OCT1<\/scp>\u2010 and <scp>NRF2<\/scp>\u2010mediated mechanisms in skeletal muscle cells"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4066-0199","authenticated-orcid":false,"given":"Shin","family":"Takasawa","sequence":"first","affiliation":[{"name":"Department of Biochemistry Nara 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