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Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin gene transcription and content in β cells.

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Τίτλος: Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin gene transcription and content in β cells.
Συγγραφείς: Seedat F; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K.; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, U.K., Kandzija N; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, U.K., Ellis MJ; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K., Jiang S; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, U.K., Sarbalina A; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, U.K., Bancroft J; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K., Drydale E; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K., Hester SS; Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K., Fischer R; Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K., Wade AN; Research in Metabolism and Endocrinology, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.; Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, U.S.A., Stefana MI; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K., Todd JA; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K., Vatish M; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, U.K.; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, U.K.
Πηγή: Clinical science (London, England : 1979) [Clin Sci (Lond)] 2024 Nov 20; Vol. 138 (22), pp. 1481-1502.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE
Imprint Name(s): Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society
Original Publication: London, Medical Research Society.
Ιατρικοί όροι (MeSH): Diabetes, Gestational*/metabolism , Diabetes, Gestational*/genetics , Insulin-Secreting Cells*/metabolism , Insulin*/metabolism , Insulin*/blood , Placenta*/metabolism , Extracellular Vesicles*/metabolism, Pregnancy ; Humans ; Female ; Transcription, Genetic ; Cell Line
Περίληψη: Insulin secretion increases progressively during pregnancy to maintain normal maternal blood glucose levels. 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 β 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 β cell line, EndoC-βH3, to investigate their effects on β-cell function in vitro. Our results indicate that human β cells internalise placental small extracellular vesicles, leading to enhanced insulin gene expression and increased insulin content within the β 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.
(© 2024 The Author(s).)
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Grant Information: Manu Vatish
Contributed Indexing: Keywords: beta cell; extracellular vesicles; gestational diabetes; insulin; placenta; pregnancy
Substance Nomenclature: 0 (Insulin)
Entry Date(s): Date Created: 20241021 Date Completed: 20241120 Latest Revision: 20260713
Update Code: 20260713
PubMed Central ID: PMC11579211
DOI: 10.1042/CS20241782
PMID: 39432712
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1470-8736
DOI:10.1042/CS20241782