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The placenta plays a crucial role in this process by releasing hormones and extracellular vesicles into the maternal circulation, which drive significant changes in pregnancy physiology. Placental extracellular vesicles, which are detectable in the plasma of pregnant women, have been shown to signal peripheral tissues and contribute to pregnancy-related conditions. While studies using murine models have demonstrated that extracellular vesicles can modulate insulin secretion in pancreatic islets, it remains unclear whether these effects translate to human biology. Understanding how placental signals enhance insulin synthesis and secretion from \u03b2 cells could be pivotal in developing new therapies for diabetes. In our study, we isolated placental small extracellular vesicles from human placentae and utilised the human \u03b2 cell line, EndoC-\u03b2H3, to investigate their effects on \u03b2-cell function in vitro. Our results indicate that human \u03b2 cells internalise placental small extracellular vesicles, leading to enhanced insulin gene expression and increased insulin content within the \u03b2 cells. Moreover, these vesicles up-regulated the expression of Annexin A1, a protein known to increase insulin content. This up-regulation of Annexin A1 holds promise as a potential mechanism by which placental small extracellular vesicles enhance insulin biosynthesis.<\/jats:p>","DOI":"10.1042\/cs20241782","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T14:16:01Z","timestamp":1729520161000},"page":"1481-1502","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin gene transcription and content in \u03b2 cells"],"prefix":"10.1042","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1352-6015","authenticated-orcid":false,"given":"Faheem","family":"Seedat","sequence":"first","affiliation":[{"name":"1Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K."},{"name":"2Nuffield Department of Women's and Reproductive Health, University of 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