Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85135148953
Pubmed ID
35902739
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Suksri K., Semprasert N., Limjindaporn T., Yenchitsomanus P.t., Kooptiwoot S., Kooptiwut S. Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-17372-z Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86406
Title
Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis
Author's Affiliation
Other Contributor(s)
Abstract
Steroid-induced diabetes is a well-known metabolic side effect of long-term use of glucocorticoid (GC). Our group recently demonstrated dexamethasone-induced pancreatic β-cell apoptosis via upregulation of TRAIL and TRAIL death receptor (DR5). Genistein protects against pancreatic β-cell apoptosis induced by toxic agents. This study aimed to investigate the cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis in cultured rat insulinoma (INS-1) cell line and in isolated mouse islets. In the absence of genistein, dexamethasone-induced pancreatic β-cell apoptosis was associated with upregulation of TRAIL, DR5, and superoxide production, but downregulation of TRAIL decoy receptor (DcR1). Dexamethasone also activated the expression of extrinsic and intrinsic apoptotic proteins, including Bax, NF-κB, caspase-8, and caspase-3, but suppressed the expression of the anti-apoptotic Bcl-2 protein. Combination treatment with dexamethasone and genistein protected against pancreatic β-cell apoptosis, and reduced the effects of dexamethasone on the expressions of TRAIL, DR5, DcR1, superoxide production, Bax, Bcl-2, NF-κB, caspase-8, and caspase-3. Moreover, combination treatment with dexamethasone and genistein reduced the expressions of TRAIL and DR5 in isolated mouse islets. The results of this study demonstrate the cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis in both cell line and islets via reduced TRAIL and DR5 protein expression.