Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection
Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L −1 , is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stres...
Gespeichert in:
| Veröffentlicht in: | Pflügers Archiv 2022, Vol.474 (1), p.83-98 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 98 |
|---|---|
| container_issue | 1 |
| container_start_page | 83 |
| container_title | Pflügers Archiv |
| container_volume | 474 |
| creator | Bahadoran, Zahra Mirmiran, Parvin Kashfi, Khosrow Ghasemi, Asghar |
| description | Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L
−1
, is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia. |
| doi_str_mv | 10.1007/s00424-021-02606-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2555638162</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2555638162</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-1807f8f2fc0f0225e2c67e35b9b9573c9aa12f10c1d465114ff705aa240daca53</originalsourceid><addsrcrecordid>eNp9kEFLHTEQx0NR6tP2C3iQBS-9bDsz2WT39SZiVRCKYM8hLztpI_uyz2QX9Nsb-54WPPQwzGF-85_hJ8QxwlcEaL9lgIaaGghLadA1fRALbCTVBCj3xAJAYq1b3R2Iw5zvAYCajj6KA9lIlB3RQtxePW04zSk4Xgdbh9jPjvuKYz9Of3gIdqhCzPMQYpU4hzzZ6Ph7VWZVDFNZq8bH0HPlxhjZTWGMn8S-t0Pmz7t-JH79uLg7v6pvfl5en5_d1E62aqqxg9Z3nrwDD0SKyemWpVotV0vVSre0FskjOOwbrRAb71tQ1lIDvXVWySPxZZu7SePDzHky65AdD4ONPM7ZkFJKyw41FfT0HXo_zimW7wxpbNUSleoKRVvKpTHnxN5sUljb9GQQzItwsxVuinDzV7h5iT7ZRc-rNfdvK6-GCyC3QC6j-JvTv9v_iX0Gl5-LFg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2617591558</pqid></control><display><type>article</type><title>Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection</title><source>MEDLINE</source><source>SpringerLink (Online service)</source><creator>Bahadoran, Zahra ; Mirmiran, Parvin ; Kashfi, Khosrow ; Ghasemi, Asghar</creator><creatorcontrib>Bahadoran, Zahra ; Mirmiran, Parvin ; Kashfi, Khosrow ; Ghasemi, Asghar</creatorcontrib><description>Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L
−1
, is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia.</description><identifier>ISSN: 0031-6768</identifier><identifier>EISSN: 1432-2013</identifier><identifier>DOI: 10.1007/s00424-021-02606-2</identifier><identifier>PMID: 34313822</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Animals ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Drug development ; Drug resistance ; Endothelial cells ; Endothelial Cells - metabolism ; Endothelium, Vascular - metabolism ; Human Physiology ; Humans ; Hyperuricemia ; Hyperuricemia - complications ; Hyperuricemia - metabolism ; Insulin ; Insulin Resistance ; Invited Review ; Kinases ; Molecular Medicine ; Neurosciences ; Nitric oxide ; Nitric Oxide - metabolism ; Nitric-oxide synthase ; Oxidative stress ; Receptors ; Signal transduction ; Uric acid ; Uric Acid - metabolism ; Vasodilation</subject><ispartof>Pflügers Archiv, 2022, Vol.474 (1), p.83-98</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-1807f8f2fc0f0225e2c67e35b9b9573c9aa12f10c1d465114ff705aa240daca53</citedby><cites>FETCH-LOGICAL-c375t-1807f8f2fc0f0225e2c67e35b9b9573c9aa12f10c1d465114ff705aa240daca53</cites><orcidid>0000-0001-6867-2151</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00424-021-02606-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00424-021-02606-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34313822$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bahadoran, Zahra</creatorcontrib><creatorcontrib>Mirmiran, Parvin</creatorcontrib><creatorcontrib>Kashfi, Khosrow</creatorcontrib><creatorcontrib>Ghasemi, Asghar</creatorcontrib><title>Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection</title><title>Pflügers Archiv</title><addtitle>Pflugers Arch - Eur J Physiol</addtitle><addtitle>Pflugers Arch</addtitle><description>Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L
−1
, is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hyperuricemia</subject><subject>Hyperuricemia - complications</subject><subject>Hyperuricemia - metabolism</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Invited Review</subject><subject>Kinases</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Oxidative stress</subject><subject>Receptors</subject><subject>Signal transduction</subject><subject>Uric acid</subject><subject>Uric Acid - metabolism</subject><subject>Vasodilation</subject><issn>0031-6768</issn><issn>1432-2013</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kEFLHTEQx0NR6tP2C3iQBS-9bDsz2WT39SZiVRCKYM8hLztpI_uyz2QX9Nsb-54WPPQwzGF-85_hJ8QxwlcEaL9lgIaaGghLadA1fRALbCTVBCj3xAJAYq1b3R2Iw5zvAYCajj6KA9lIlB3RQtxePW04zSk4Xgdbh9jPjvuKYz9Of3gIdqhCzPMQYpU4hzzZ6Ph7VWZVDFNZq8bH0HPlxhjZTWGMn8S-t0Pmz7t-JH79uLg7v6pvfl5en5_d1E62aqqxg9Z3nrwDD0SKyemWpVotV0vVSre0FskjOOwbrRAb71tQ1lIDvXVWySPxZZu7SePDzHky65AdD4ONPM7ZkFJKyw41FfT0HXo_zimW7wxpbNUSleoKRVvKpTHnxN5sUljb9GQQzItwsxVuinDzV7h5iT7ZRc-rNfdvK6-GCyC3QC6j-JvTv9v_iX0Gl5-LFg</recordid><startdate>2022</startdate><enddate>2022</enddate><creator>Bahadoran, Zahra</creator><creator>Mirmiran, Parvin</creator><creator>Kashfi, Khosrow</creator><creator>Ghasemi, Asghar</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6867-2151</orcidid></search><sort><creationdate>2022</creationdate><title>Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection</title><author>Bahadoran, Zahra ; Mirmiran, Parvin ; Kashfi, Khosrow ; Ghasemi, Asghar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-1807f8f2fc0f0225e2c67e35b9b9573c9aa12f10c1d465114ff705aa240daca53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Drug development</topic><topic>Drug resistance</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hyperuricemia</topic><topic>Hyperuricemia - complications</topic><topic>Hyperuricemia - metabolism</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Invited Review</topic><topic>Kinases</topic><topic>Molecular Medicine</topic><topic>Neurosciences</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric-oxide synthase</topic><topic>Oxidative stress</topic><topic>Receptors</topic><topic>Signal transduction</topic><topic>Uric acid</topic><topic>Uric Acid - metabolism</topic><topic>Vasodilation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bahadoran, Zahra</creatorcontrib><creatorcontrib>Mirmiran, Parvin</creatorcontrib><creatorcontrib>Kashfi, Khosrow</creatorcontrib><creatorcontrib>Ghasemi, Asghar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science 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>MEDLINE - Academic</collection><jtitle>Pflügers Archiv</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bahadoran, Zahra</au><au>Mirmiran, Parvin</au><au>Kashfi, Khosrow</au><au>Ghasemi, Asghar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection</atitle><jtitle>Pflügers Archiv</jtitle><stitle>Pflugers Arch - Eur J Physiol</stitle><addtitle>Pflugers Arch</addtitle><date>2022</date><risdate>2022</risdate><volume>474</volume><issue>1</issue><spage>83</spage><epage>98</epage><pages>83-98</pages><issn>0031-6768</issn><eissn>1432-2013</eissn><abstract>Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L
−1
, is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34313822</pmid><doi>10.1007/s00424-021-02606-2</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-6867-2151</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-6768 |
| ispartof | Pflügers Archiv, 2022, Vol.474 (1), p.83-98 |
| issn | 0031-6768 1432-2013 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2555638162 |
| source | MEDLINE; SpringerLink (Online service) |
| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Animals Apoptosis Biomedical and Life Sciences Biomedicine Cell Biology Drug development Drug resistance Endothelial cells Endothelial Cells - metabolism Endothelium, Vascular - metabolism Human Physiology Humans Hyperuricemia Hyperuricemia - complications Hyperuricemia - metabolism Insulin Insulin Resistance Invited Review Kinases Molecular Medicine Neurosciences Nitric oxide Nitric Oxide - metabolism Nitric-oxide synthase Oxidative stress Receptors Signal transduction Uric acid Uric Acid - metabolism Vasodilation |
| title | Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T22%3A21%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hyperuricemia-induced%20endothelial%20insulin%20resistance:%20the%20nitric%20oxide%20connection&rft.jtitle=Pfl%C3%BCgers%20Archiv&rft.au=Bahadoran,%20Zahra&rft.date=2022&rft.volume=474&rft.issue=1&rft.spage=83&rft.epage=98&rft.pages=83-98&rft.issn=0031-6768&rft.eissn=1432-2013&rft_id=info:doi/10.1007/s00424-021-02606-2&rft_dat=%3Cproquest_cross%3E2555638162%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2617591558&rft_id=info:pmid/34313822&rfr_iscdi=true |