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Sex\u2010biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory\u2013islet crosstalk. However, the molecular underpinnings of these male\u2013female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex\u2010biased insulin sensing\u2010 and\/or insulin secretion\u2010modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5\u201012 DRG sensory neurons derived from sexually immature 3\u2010week\u2010old male and female C57BL\/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. The transcriptome analysis identified, among others, higher insulin signaling\/sensing capabilities in female DRG neurons; secretome screening uncovered several sex\u2010specific candidate molecules with potential regulatory functions in pancreatic \u03b2 cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG\u2013islet crosstalk with implications in sensory feedback loops in the regulation of \u03b2\u2010cell activity in a sex\u2010biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies\/approaches to fathom the role of the sensory\u2013islet axis in the regulation of energy balance in males and females.<\/jats:p>","DOI":"10.1096\/fj.202300941r","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T12:39:25Z","timestamp":1694435965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptome and secretome profiling of sensory neurons reveals sex differences in pathways relevant to insulin sensing and insulin secretion"],"prefix":"10.1096","volume":"37","author":[{"given":"Sohyun","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences New York Institute of Technology College of Osteopathic Medicine  Old Westbury New York 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