Glucocorticoid-mediated induction of ZBTB16 affects insulin secretion in human islets and EndoC-βH1 β-cells.

Autor:	Karagiannopoulos A; Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.; Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden., Westholm E; Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.; Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden., Ofori JK; Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.; Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden.; Epigenetic and Diabetes, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden., Cowan E; Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.; Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden., Esguerra JLS; Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.; Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden.; Novo Nordisk A/S, Copenhagen, Denmark., Eliasson L; Islet Cell Exocytosis, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.; Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Apr 01; Vol. 26 (5), pp. 106555. Date of Electronic Publication: 2023 Apr 01 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106555
Abstrakt:	Glucocorticoid use is associated with steroid-induced diabetes mellitus and impaired pancreatic β-cell insulin secretion. Here, the glucocorticoid-mediated transcriptomic changes in human pancreatic islets and the human insulin-secreting EndoC-βH1 cells were investigated to uncover genes involved in β-cell steroid stress-response processes. Bioinformatics analysis revealed glucocorticoids to exert their effects mainly on enhancer genomic regions in collaboration with auxiliary transcription factor families including AP-1, ETS/TEAD, and FOX. Remarkably, we identified the transcription factor ZBTB16 as a highly confident direct glucocorticoid target. Glucocorticoid-mediated induction of ZBTB16 was time- and dose-dependent. Manipulation of ZBTB16 expression in EndoC-βH1 cells combined with dexamethasone treatment demonstrated its protective role against glucocorticoid-induced reduction of insulin secretion and mitochondrial function impairment. In conclusion, we determine the molecular impact of glucocorticoids on human islets and insulin-secreting cells and investigate the effects of glucocorticoid targets on β-cell function. Our findings can pave the way for therapies against steroid-induced diabetes mellitus. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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