Transcriptional regulation of insulin receptor gene promoter in rat hepatocytes.

摘要: Abstract To investigate the DNA regulatory sequences −618 to −593 (initiator ATG is +1) of insulin receptor (IR) promoter required for IR gene expression, primary cultured hepatocytes rats were transfected with plasmids containing 5′-flanking rat fused luciferase gene. When three copies nucleotides transfected, reporter activity was significantly increased in presence glucose and more glucose/insulin. The glucose/insulin stimulation inhibited by addition polyunsaturated fatty acids. These results similar those found earlier transcriptions acid synthase, FAS(−57/−35), ATP citrate-lyase, ACL(−64/−41), leptin(−101/−83) genes, which have a high similarity IR(−618/−593). However, similarly leptin gene, responsive than FAS ACL genes. Mutation either one Sp1 binding sites (−618/−593) did not affect transcription, whereas mutation or four resulted loss responsiveness Gel mobility shift assays revealed that nuclear factor(s) from liver specifically formed complexes sequence By antibody supershift assays, transcription factors Sp1and Sp3 bind IR, leptin, genes contain common DNA-sequences responsible glucose/insulin-stimulation, suggesting these are regulated.