Glucocorticoid-mediated induction of ZBTB16 affects insulin secretion in human islets and EndoC-βH1 β-cells
(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
(Less)
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.
- author
- Karagiannopoulos, Alexandros LU ; Westholm, Efraim LU ; Ofori, Jones K LU ; Cowan, Elaine LU ; Esguerra, Jonathan L S LU and Eliasson, Lena LU
- organization
- publishing date
- 2023-05-19
- type
- Contribution to journal
- publication status
- published
- subject
- in
- iScience
- volume
- 26
- issue
- 5
- article number
- 106555
- pages
- 1 - 23
- publisher
- Elsevier
- external identifiers
-
- pmid:37250333
- scopus:85152567756
- 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
- 2024-12-14 23:34:38
@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}}, }