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

Autor:	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.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2024 Nov 20; Vol. 138 (22), pp. 1481-1502.
DOI:	10.1042/CS20241782
Abstrakt:	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).)
Databáze:	MEDLINE
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