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Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway
BACKGROUND: Recent studies have shown that the accumulation of free iron and lipid peroxides will trigger a new form of cell death—ferroptosis. This form of cell death is associated with a variety of diseases, including type 2 diabetes. We hypothesize that iron overload may play a role in driving gl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120586/ https://www.ncbi.nlm.nih.gov/pubmed/37090106 http://dx.doi.org/10.7717/peerj.15206 |
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author | Deng, Ling Mo, Man-Qiu Zhong, Jinling Li, Zhengming Li, Guoqiao Liang, Yuzhen |
author_facet | Deng, Ling Mo, Man-Qiu Zhong, Jinling Li, Zhengming Li, Guoqiao Liang, Yuzhen |
author_sort | Deng, Ling |
collection | PubMed |
description | BACKGROUND: Recent studies have shown that the accumulation of free iron and lipid peroxides will trigger a new form of cell death—ferroptosis. This form of cell death is associated with a variety of diseases, including type 2 diabetes. We hypothesize that iron overload may play a role in driving glucose metabolism abnormalities by inducing endoplasmic reticulum stress that mediates ferroptosis in islet β cells. In this study, we tested this conjecture from in vivo and in vitro experiments. METHODS: We established a mouse iron overload model by intraperitoneal injection of iron dextrose (50 mg/kg) and an iron overload cell model by treating MIN6 cells with ferric ammonium citrate (640 μmol/L, 48 h) in vitro. The iron deposition in pancreatic tissue was observed by Prussian blue staining, and the pathological changes in pancreatic tissues by HE staining and the protein expression level by pancreatic immunohistochemistry. In the cellular experiments, we detected the cell viability by CCK8 and observed the cellular ultrastructure by transmission electron microscopy. We also used MDA and ROS kits to detect the level of oxidative stress and lipid peroxidation in cells. Western blotting was performed to detect the expression levels of target proteins. RESULTS: Iron overload induces MIN6 cell dysfunction, leading to increased fasting blood glucose, impaired glucose tolerance, and significantly decreased insulin sensitivity in mice. This process may be related to the ferroptosis of islet β cells and the activation of ASK1/P-P38/CHOP signaling pathway. |
format | Online Article Text |
id | pubmed-10120586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101205862023-04-22 Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway Deng, Ling Mo, Man-Qiu Zhong, Jinling Li, Zhengming Li, Guoqiao Liang, Yuzhen PeerJ Diabetes and Endocrinology BACKGROUND: Recent studies have shown that the accumulation of free iron and lipid peroxides will trigger a new form of cell death—ferroptosis. This form of cell death is associated with a variety of diseases, including type 2 diabetes. We hypothesize that iron overload may play a role in driving glucose metabolism abnormalities by inducing endoplasmic reticulum stress that mediates ferroptosis in islet β cells. In this study, we tested this conjecture from in vivo and in vitro experiments. METHODS: We established a mouse iron overload model by intraperitoneal injection of iron dextrose (50 mg/kg) and an iron overload cell model by treating MIN6 cells with ferric ammonium citrate (640 μmol/L, 48 h) in vitro. The iron deposition in pancreatic tissue was observed by Prussian blue staining, and the pathological changes in pancreatic tissues by HE staining and the protein expression level by pancreatic immunohistochemistry. In the cellular experiments, we detected the cell viability by CCK8 and observed the cellular ultrastructure by transmission electron microscopy. We also used MDA and ROS kits to detect the level of oxidative stress and lipid peroxidation in cells. Western blotting was performed to detect the expression levels of target proteins. RESULTS: Iron overload induces MIN6 cell dysfunction, leading to increased fasting blood glucose, impaired glucose tolerance, and significantly decreased insulin sensitivity in mice. This process may be related to the ferroptosis of islet β cells and the activation of ASK1/P-P38/CHOP signaling pathway. PeerJ Inc. 2023-04-18 /pmc/articles/PMC10120586/ /pubmed/37090106 http://dx.doi.org/10.7717/peerj.15206 Text en © 2023 Deng et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Diabetes and Endocrinology Deng, Ling Mo, Man-Qiu Zhong, Jinling Li, Zhengming Li, Guoqiao Liang, Yuzhen Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway |
title | Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway |
title_full | Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway |
title_fullStr | Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway |
title_full_unstemmed | Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway |
title_short | Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway |
title_sort | iron overload induces islet β cell ferroptosis by activating ask1/p-p38/chop signaling pathway |
topic | Diabetes and Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120586/ https://www.ncbi.nlm.nih.gov/pubmed/37090106 http://dx.doi.org/10.7717/peerj.15206 |
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