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

Karagiannopoulos, Alexandros LU orcid ; Westholm, Efraim LU ; Ofori, Jones K LU ; Cowan, Elaine LU orcid ; Esguerra, Jonathan L S LU orcid and Eliasson, Lena LU orcid (2023) In iScience 26(5). p.1-23
Abstract

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.... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
iScience
volume
26
issue
5
article number
106555
pages
1 - 23
publisher
Elsevier
external identifiers
  • scopus:85152567756
  • pmid:37250333
ISSN
2589-0042
DOI
10.1016/j.isci.2023.106555
language
English
LU publication?
yes
additional info
© 2023 The Author(s).
id
98f5f10c-83c9-4edf-bafb-095305e8af56
date added to LUP
2023-05-31 12:12:37
date last changed
2025-10-20 09:59:59
@article{98f5f10c-83c9-4edf-bafb-095305e8af56,
  abstract     = {{<p>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 <br>
 ZBTB16 as a highly confident direct glucocorticoid target. Glucocorticoid-mediated induction of <br>
 ZBTB16 was time- and dose-dependent. Manipulation of <br>
 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.<br>
 </p>}},
  author       = {{Karagiannopoulos, Alexandros and Westholm, Efraim and Ofori, Jones K and Cowan, Elaine and Esguerra, Jonathan L S and Eliasson, Lena}},
  issn         = {{2589-0042}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  pages        = {{1--23}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Glucocorticoid-mediated induction of ZBTB16 affects insulin secretion in human islets and EndoC-βH1 β-cells}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2023.106555}},
  doi          = {{10.1016/j.isci.2023.106555}},
  volume       = {{26}},
  year         = {{2023}},
}