Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells
Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic β-cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to tre...
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Veröffentlicht in: | Evidence-based complementary and alternative medicine 2023, Vol.2023 (1), p.9428241-9428241 |
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description | Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic β-cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to treat T2DM. Ferroptosis is a newly identified form of cell death that has distinct features. However, knowledge regarding the role of ferroptosis in the death of PBCs remains limited. In the current study, we used high glucose (10 mM) (HG) levels to induce ferroptosis in PBC. We also observed that hispidin, a polyphenol compound that can be isolated from Phellinus linteus, could attenuate ferroptosis induced by HG in PBCs. Mechanistic investigations showed that hispidin led to the upregulation of miR-15b-5p, which directly inhibits the expression of glutaminase (GLS2) which plays an essential role in the glutamine metabolism. In addition, we found that overexpression of GLS2 could abrogate the protective effect of hispidin against ferroptosis caused by HG in PBCs. Therefore, our study provides novel insights into the mechanisms that regulate the death of PBCs. |
doi_str_mv | 10.1155/2023/9428241 |
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O.</contributor><creatorcontrib>Wu, Fang ; Shang, Chenxin ; Jin, Ting ; Shi, Linhui ; Ajiboye, B. O.</creatorcontrib><description>Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic β-cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to treat T2DM. Ferroptosis is a newly identified form of cell death that has distinct features. However, knowledge regarding the role of ferroptosis in the death of PBCs remains limited. In the current study, we used high glucose (10 mM) (HG) levels to induce ferroptosis in PBC. We also observed that hispidin, a polyphenol compound that can be isolated from Phellinus linteus, could attenuate ferroptosis induced by HG in PBCs. Mechanistic investigations showed that hispidin led to the upregulation of miR-15b-5p, which directly inhibits the expression of glutaminase (GLS2) which plays an essential role in the glutamine metabolism. In addition, we found that overexpression of GLS2 could abrogate the protective effect of hispidin against ferroptosis caused by HG in PBCs. Therefore, our study provides novel insights into the mechanisms that regulate the death of PBCs.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2023/9428241</identifier><identifier>PMID: 36865751</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Apoptosis ; Autophagy ; Beta cells ; Cell death ; Cells ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Ferroptosis ; Glucose ; Glutaminase ; Glutamine ; MicroRNAs ; Pancreas ; Public health ; Reagents</subject><ispartof>Evidence-based complementary and alternative medicine, 2023, Vol.2023 (1), p.9428241-9428241</ispartof><rights>Copyright © 2023 Fang Wu et al.</rights><rights>Copyright © 2023 Fang Wu et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2023 Fang Wu et al. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3631-975ebe0e9ac8a7702a157c2d8912d6cfc970182d5cb7342d8ac4226260d83fe83</citedby><cites>FETCH-LOGICAL-c3631-975ebe0e9ac8a7702a157c2d8912d6cfc970182d5cb7342d8ac4226260d83fe83</cites><orcidid>0000-0001-5760-5105 ; 0000-0002-6311-3868 ; 0000-0003-0590-698X ; 0000-0001-9669-7970</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974274/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974274/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36865751$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ajiboye, B. O.</contributor><creatorcontrib>Wu, Fang</creatorcontrib><creatorcontrib>Shang, Chenxin</creatorcontrib><creatorcontrib>Jin, Ting</creatorcontrib><creatorcontrib>Shi, Linhui</creatorcontrib><title>Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic β-cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to treat T2DM. Ferroptosis is a newly identified form of cell death that has distinct features. However, knowledge regarding the role of ferroptosis in the death of PBCs remains limited. In the current study, we used high glucose (10 mM) (HG) levels to induce ferroptosis in PBC. We also observed that hispidin, a polyphenol compound that can be isolated from Phellinus linteus, could attenuate ferroptosis induced by HG in PBCs. Mechanistic investigations showed that hispidin led to the upregulation of miR-15b-5p, which directly inhibits the expression of glutaminase (GLS2) which plays an essential role in the glutamine metabolism. In addition, we found that overexpression of GLS2 could abrogate the protective effect of hispidin against ferroptosis caused by HG in PBCs. Therefore, our study provides novel insights into the mechanisms that regulate the death of PBCs.</description><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Beta cells</subject><subject>Cell death</subject><subject>Cells</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Ferroptosis</subject><subject>Glucose</subject><subject>Glutaminase</subject><subject>Glutamine</subject><subject>MicroRNAs</subject><subject>Pancreas</subject><subject>Public health</subject><subject>Reagents</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kUtrGzEUhUVoyKvZdV0E2QSSifUYjaRNITGNHTCk9AHZCY0kZ5SOR1NpJm3-fWXsmjaLrnR176fDPToAvMPoCmPGJgQROpElEaTEe-AI8xIX-Sbe7Gr-cAiOU3pCiEjO-QE4pJWoGGf4CHyf-9R76zt41zW-9kOCty7G0A8h-ZSbdjTOwvoFzv1jA2ftaEJy8NlrODQOrvznArO6YP1ktvhC4PWv_CiLfdKdiU4P3sAbN2g4dW2b3oL9pW6TO92eJ-Db7cev03mxuJ_dTa8XhaEVxYXkzNUOOamN0JwjojHjhlghMbGVWRrJERbEMlNzWua-NiUhFamQFXTpBD0BHza6_VivnDWuG6JuVR_9SscXFbRX_04636jH8Kyk5Pm3yixwvhWI4cfo0qBWPplsQXcujEkRLmgpMcYoo2ev0Kcwxi7bW1M5FFJRmqnLDWViSCm65W4ZjNQ6RbVOUW1TzPj7vw3s4D-xZeBiAzS-s_qn_7_cbyadotE</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Wu, Fang</creator><creator>Shang, Chenxin</creator><creator>Jin, Ting</creator><creator>Shi, Linhui</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5760-5105</orcidid><orcidid>https://orcid.org/0000-0002-6311-3868</orcidid><orcidid>https://orcid.org/0000-0003-0590-698X</orcidid><orcidid>https://orcid.org/0000-0001-9669-7970</orcidid></search><sort><creationdate>2023</creationdate><title>Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells</title><author>Wu, Fang ; Shang, Chenxin ; Jin, Ting ; Shi, Linhui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3631-975ebe0e9ac8a7702a157c2d8912d6cfc970182d5cb7342d8ac4226260d83fe83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Beta cells</topic><topic>Cell death</topic><topic>Cells</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Ferroptosis</topic><topic>Glucose</topic><topic>Glutaminase</topic><topic>Glutamine</topic><topic>MicroRNAs</topic><topic>Pancreas</topic><topic>Public health</topic><topic>Reagents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Fang</creatorcontrib><creatorcontrib>Shang, Chenxin</creatorcontrib><creatorcontrib>Jin, Ting</creatorcontrib><creatorcontrib>Shi, Linhui</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest Psychology Journals</collection><collection>ProQuest Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Evidence-based complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Fang</au><au>Shang, Chenxin</au><au>Jin, Ting</au><au>Shi, Linhui</au><au>Ajiboye, B. O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><addtitle>Evid Based Complement Alternat Med</addtitle><date>2023</date><risdate>2023</risdate><volume>2023</volume><issue>1</issue><spage>9428241</spage><epage>9428241</epage><pages>9428241-9428241</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic β-cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to treat T2DM. Ferroptosis is a newly identified form of cell death that has distinct features. However, knowledge regarding the role of ferroptosis in the death of PBCs remains limited. In the current study, we used high glucose (10 mM) (HG) levels to induce ferroptosis in PBC. We also observed that hispidin, a polyphenol compound that can be isolated from Phellinus linteus, could attenuate ferroptosis induced by HG in PBCs. Mechanistic investigations showed that hispidin led to the upregulation of miR-15b-5p, which directly inhibits the expression of glutaminase (GLS2) which plays an essential role in the glutamine metabolism. In addition, we found that overexpression of GLS2 could abrogate the protective effect of hispidin against ferroptosis caused by HG in PBCs. Therefore, our study provides novel insights into the mechanisms that regulate the death of PBCs.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>36865751</pmid><doi>10.1155/2023/9428241</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5760-5105</orcidid><orcidid>https://orcid.org/0000-0002-6311-3868</orcidid><orcidid>https://orcid.org/0000-0003-0590-698X</orcidid><orcidid>https://orcid.org/0000-0001-9669-7970</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Apoptosis Autophagy Beta cells Cell death Cells Diabetes Diabetes mellitus (non-insulin dependent) Ferroptosis Glucose Glutaminase Glutamine MicroRNAs Pancreas Public health Reagents |
title | Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells |
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