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Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis
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 i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334585/ https://www.ncbi.nlm.nih.gov/pubmed/35902739 http://dx.doi.org/10.1038/s41598-022-17372-z |
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author | Suksri, Kanchana Semprasert, Namoiy Limjindaporn, Thawornchai Yenchitsomanus, Pa-thai Kooptiwoot, Sirirat Kooptiwut, Suwattanee |
author_facet | Suksri, Kanchana Semprasert, Namoiy Limjindaporn, Thawornchai Yenchitsomanus, Pa-thai Kooptiwoot, Sirirat Kooptiwut, Suwattanee |
author_sort | Suksri, Kanchana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9334585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93345852022-07-30 Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis Suksri, Kanchana Semprasert, Namoiy Limjindaporn, Thawornchai Yenchitsomanus, Pa-thai Kooptiwoot, Sirirat Kooptiwut, Suwattanee Sci Rep Article 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. Nature Publishing Group UK 2022-07-28 /pmc/articles/PMC9334585/ /pubmed/35902739 http://dx.doi.org/10.1038/s41598-022-17372-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Suksri, Kanchana Semprasert, Namoiy Limjindaporn, Thawornchai Yenchitsomanus, Pa-thai Kooptiwoot, Sirirat Kooptiwut, Suwattanee Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
title | Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
title_full | Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
title_fullStr | Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
title_full_unstemmed | Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
title_short | Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
title_sort | cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334585/ https://www.ncbi.nlm.nih.gov/pubmed/35902739 http://dx.doi.org/10.1038/s41598-022-17372-z |
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