p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance
The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower...
Gespeichert in:
Veröffentlicht in: | Nephrology, dialysis, transplantation dialysis, transplantation, 2017-12, Vol.32 (12), p.2000-2009 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2009 |
---|---|
container_issue | 12 |
container_start_page | 2000 |
container_title | Nephrology, dialysis, transplantation |
container_volume | 32 |
creator | Koppe, Laetitia Alix, Pascaline M Croze, Marine L Chambert, Stéphane Vanholder, Raymond Glorieux, Griet Fouque, Denis Soulage, Christophe O |
description | The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism.
p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot.
In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and |
doi_str_mv | 10.1093/ndt/gfx089 |
format | Article |
fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01829774v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1949693306</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-4ba4b4e9d7be937f1f8d67af25cc28e7dfcecdf17b9d106b4b0f5ec09878aabd3</originalsourceid><addsrcrecordid>eNpNkU1PXCEUhklTU0fbTX-AYVlNr8L94tLdZKLVZBI37ZrwcVAM9zIC19Tf0j8r40ytK8g5z3kg50XoKyXnlPDmYjL54s7-IQP_gBa07UlVN0P3ES1Kk1akI_wQHaX0QAjhNWOf0GE9cF4XfoH-bqpVhPTs8Z2f9RzD5Axgl7DEo3wIEY-QpQreZcDB4k2lCx08dhMew5zgx_amw5SjTBnnsCeKL81-cy8zfP9fev-Elc6n14EYxlDsbioTRVZQl7KcNHxGB1b6BF_25zH6fXX5a3VdrW9_3qyW60o3HctVq2SrWuCGKeANs9QOpmfS1p3W9QDMWA3aWMoUN5T0qlXEdqAJH9ggpTLNMTrdee-lF5voRhmfRZBOXC_XYlsjdKg5Y-0TLey3HVu-_ThDymJ0SYP3coKyD0F5y3veNKQv6NkO1TGkFMG-uSkR2-BECU7sgivwyd47qxHMG_ovqeYFwxGZDA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1949693306</pqid></control><display><type>article</type><title>p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance</title><source>MEDLINE</source><source>Oxford Journals - Connect here FIRST to enable access</source><source>Free E-Journal (出版社公開部分のみ)</source><source>Alma/SFX Local Collection</source><creator>Koppe, Laetitia ; Alix, Pascaline M ; Croze, Marine L ; Chambert, Stéphane ; Vanholder, Raymond ; Glorieux, Griet ; Fouque, Denis ; Soulage, Christophe O</creator><creatorcontrib>Koppe, Laetitia ; Alix, Pascaline M ; Croze, Marine L ; Chambert, Stéphane ; Vanholder, Raymond ; Glorieux, Griet ; Fouque, Denis ; Soulage, Christophe O</creatorcontrib><description>The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism.
p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot.
In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and <6% for p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS.
The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfx089</identifier><identifier>PMID: 28992089</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Cresols - blood ; Cresols - pharmacology ; Glucuronides - blood ; Glucuronides - pharmacology ; Insulin - metabolism ; Insulin Resistance ; Life Sciences ; Mice ; Renal Insufficiency, Chronic - drug therapy ; Renal Insufficiency, Chronic - physiopathology ; Signal Transduction - drug effects ; Sulfuric Acid Esters - blood ; Sulfuric Acid Esters - pharmacology</subject><ispartof>Nephrology, dialysis, transplantation, 2017-12, Vol.32 (12), p.2000-2009</ispartof><rights>The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-4ba4b4e9d7be937f1f8d67af25cc28e7dfcecdf17b9d106b4b0f5ec09878aabd3</citedby><cites>FETCH-LOGICAL-c357t-4ba4b4e9d7be937f1f8d67af25cc28e7dfcecdf17b9d106b4b0f5ec09878aabd3</cites><orcidid>0000-0002-5076-2420 ; 0000-0002-9707-7199 ; 0000-0003-2633-1636 ; 0000-0002-7641-4707</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28992089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01829774$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Koppe, Laetitia</creatorcontrib><creatorcontrib>Alix, Pascaline M</creatorcontrib><creatorcontrib>Croze, Marine L</creatorcontrib><creatorcontrib>Chambert, Stéphane</creatorcontrib><creatorcontrib>Vanholder, Raymond</creatorcontrib><creatorcontrib>Glorieux, Griet</creatorcontrib><creatorcontrib>Fouque, Denis</creatorcontrib><creatorcontrib>Soulage, Christophe O</creatorcontrib><title>p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol Dial Transplant</addtitle><description>The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism.
p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot.
In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and <6% for p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS.
The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD.</description><subject>Animals</subject><subject>Cresols - blood</subject><subject>Cresols - pharmacology</subject><subject>Glucuronides - blood</subject><subject>Glucuronides - pharmacology</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Renal Insufficiency, Chronic - drug therapy</subject><subject>Renal Insufficiency, Chronic - physiopathology</subject><subject>Signal Transduction - drug effects</subject><subject>Sulfuric Acid Esters - blood</subject><subject>Sulfuric Acid Esters - pharmacology</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkU1PXCEUhklTU0fbTX-AYVlNr8L94tLdZKLVZBI37ZrwcVAM9zIC19Tf0j8r40ytK8g5z3kg50XoKyXnlPDmYjL54s7-IQP_gBa07UlVN0P3ES1Kk1akI_wQHaX0QAjhNWOf0GE9cF4XfoH-bqpVhPTs8Z2f9RzD5Axgl7DEo3wIEY-QpQreZcDB4k2lCx08dhMew5zgx_amw5SjTBnnsCeKL81-cy8zfP9fev-Elc6n14EYxlDsbioTRVZQl7KcNHxGB1b6BF_25zH6fXX5a3VdrW9_3qyW60o3HctVq2SrWuCGKeANs9QOpmfS1p3W9QDMWA3aWMoUN5T0qlXEdqAJH9ggpTLNMTrdee-lF5voRhmfRZBOXC_XYlsjdKg5Y-0TLey3HVu-_ThDymJ0SYP3coKyD0F5y3veNKQv6NkO1TGkFMG-uSkR2-BECU7sgivwyd47qxHMG_ovqeYFwxGZDA</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Koppe, Laetitia</creator><creator>Alix, Pascaline M</creator><creator>Croze, Marine L</creator><creator>Chambert, Stéphane</creator><creator>Vanholder, Raymond</creator><creator>Glorieux, Griet</creator><creator>Fouque, Denis</creator><creator>Soulage, Christophe O</creator><general>Oxford University Press</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>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-5076-2420</orcidid><orcidid>https://orcid.org/0000-0002-9707-7199</orcidid><orcidid>https://orcid.org/0000-0003-2633-1636</orcidid><orcidid>https://orcid.org/0000-0002-7641-4707</orcidid></search><sort><creationdate>20171201</creationdate><title>p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance</title><author>Koppe, Laetitia ; Alix, Pascaline M ; Croze, Marine L ; Chambert, Stéphane ; Vanholder, Raymond ; Glorieux, Griet ; Fouque, Denis ; Soulage, Christophe O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-4ba4b4e9d7be937f1f8d67af25cc28e7dfcecdf17b9d106b4b0f5ec09878aabd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Cresols - blood</topic><topic>Cresols - pharmacology</topic><topic>Glucuronides - blood</topic><topic>Glucuronides - pharmacology</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Renal Insufficiency, Chronic - drug therapy</topic><topic>Renal Insufficiency, Chronic - physiopathology</topic><topic>Signal Transduction - drug effects</topic><topic>Sulfuric Acid Esters - blood</topic><topic>Sulfuric Acid Esters - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koppe, Laetitia</creatorcontrib><creatorcontrib>Alix, Pascaline M</creatorcontrib><creatorcontrib>Croze, Marine L</creatorcontrib><creatorcontrib>Chambert, Stéphane</creatorcontrib><creatorcontrib>Vanholder, Raymond</creatorcontrib><creatorcontrib>Glorieux, Griet</creatorcontrib><creatorcontrib>Fouque, Denis</creatorcontrib><creatorcontrib>Soulage, Christophe O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koppe, Laetitia</au><au>Alix, Pascaline M</au><au>Croze, Marine L</au><au>Chambert, Stéphane</au><au>Vanholder, Raymond</au><au>Glorieux, Griet</au><au>Fouque, Denis</au><au>Soulage, Christophe O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><addtitle>Nephrol Dial Transplant</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>32</volume><issue>12</issue><spage>2000</spage><epage>2009</epage><pages>2000-2009</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><abstract>The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism.
p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot.
In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and <6% for p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS.
The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>28992089</pmid><doi>10.1093/ndt/gfx089</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5076-2420</orcidid><orcidid>https://orcid.org/0000-0002-9707-7199</orcidid><orcidid>https://orcid.org/0000-0003-2633-1636</orcidid><orcidid>https://orcid.org/0000-0002-7641-4707</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0931-0509 |
ispartof | Nephrology, dialysis, transplantation, 2017-12, Vol.32 (12), p.2000-2009 |
issn | 0931-0509 1460-2385 |
language | eng |
recordid | cdi_hal_primary_oai_HAL_hal_01829774v1 |
source | MEDLINE; Oxford Journals - Connect here FIRST to enable access; Free E-Journal (出版社公開部分のみ); Alma/SFX Local Collection |
subjects | Animals Cresols - blood Cresols - pharmacology Glucuronides - blood Glucuronides - pharmacology Insulin - metabolism Insulin Resistance Life Sciences Mice Renal Insufficiency, Chronic - drug therapy Renal Insufficiency, Chronic - physiopathology Signal Transduction - drug effects Sulfuric Acid Esters - blood Sulfuric Acid Esters - pharmacology |
title | p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T07%3A05%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=p-Cresyl%20glucuronide%20is%20a%20major%20metabolite%20of%20p-cresol%20in%20mouse:%20in%20contrast%20to%20p-cresyl%20sulphate,%20p-cresyl%20glucuronide%20fails%20to%20promote%20insulin%20resistance&rft.jtitle=Nephrology,%20dialysis,%20transplantation&rft.au=Koppe,%20Laetitia&rft.date=2017-12-01&rft.volume=32&rft.issue=12&rft.spage=2000&rft.epage=2009&rft.pages=2000-2009&rft.issn=0931-0509&rft.eissn=1460-2385&rft_id=info:doi/10.1093/ndt/gfx089&rft_dat=%3Cproquest_hal_p%3E1949693306%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1949693306&rft_id=info:pmid/28992089&rfr_iscdi=true |