Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling
Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling Anne-Laure Colombani 1 , Lionel Carneiro 1 , Alexandre Benani 1 , Anne Galinier 1 , Tristan Jaillard 1 , Thibaut Duparc 1 , Géraldine Offer 1 , Anne Lorsignol 1 , Christophe Magnan 2 , Louis Casteilla 1 , Luc Pénicaud 1...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2009-10, Vol.58 (10), p.2189-2197 |
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| creator | COLOMBANI, Anne-Laure CARNEIRO, Lionel PENICAUD, Luc LELOUP, Corinne BENANI, Alexandre GALINIER, Anne JAILLARD, Tristan DUPARC, Thibaut OFFER, Géraldine LORSIGNOL, Anne MAGNAN, Christophe CASTEILLA, Louis |
| description | Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling
Anne-Laure Colombani 1 ,
Lionel Carneiro 1 ,
Alexandre Benani 1 ,
Anne Galinier 1 ,
Tristan Jaillard 1 ,
Thibaut Duparc 1 ,
Géraldine Offer 1 ,
Anne Lorsignol 1 ,
Christophe Magnan 2 ,
Louis Casteilla 1 ,
Luc Pénicaud 1 and
Corinne Leloup 1
1 Métabolisme, Plasticité et Mitochondrie, Unité Mixte de Recherche 5241, Centre National de la Recherche Scientifique, Université
Paul Sabatier, Toulouse, France;
2 Physiopathologie de la Nutrition, Unité Mixte de Recherche 7059, Centre National de la Recherche Scientifique, Université
Denis Diderot, Paris, France.
Corresponding author: Corinne Leloup, leloup{at}cict.fr .
Abstract
OBJECTIVE Recent data demonstrated that glucose sensing in different tissues is initiated by an intracellular redox signaling pathway
in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the
present study was to determine whether brain glucose hypersensitivity present in obese Zücker rats is related to an alteration
in redox signaling.
RESEARCH DESIGN AND METHODS Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus,
changes in reactive oxygen species levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications
of redox state and mitochondrial functions were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide
dismutase, aconitase activities, and mitochondrial respiration.
RESULTS Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased
insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated
with 1 ) increased reactive oxygen species levels in response to this low glucose load, 2 ) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial
level, and 3 ) overexpression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial
activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced glutathione infusion
in the third ventricle fully reversed the cerebral hypersensitivity to glucose.
CONCLUSIONS The data demonstrated that obese Zücker rats' impaired hypothalamic regulation in terms |
| doi_str_mv | 10.2337/db09-0110 |
| format | Article |
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Anne-Laure Colombani 1 ,
Lionel Carneiro 1 ,
Alexandre Benani 1 ,
Anne Galinier 1 ,
Tristan Jaillard 1 ,
Thibaut Duparc 1 ,
Géraldine Offer 1 ,
Anne Lorsignol 1 ,
Christophe Magnan 2 ,
Louis Casteilla 1 ,
Luc Pénicaud 1 and
Corinne Leloup 1
1 Métabolisme, Plasticité et Mitochondrie, Unité Mixte de Recherche 5241, Centre National de la Recherche Scientifique, Université
Paul Sabatier, Toulouse, France;
2 Physiopathologie de la Nutrition, Unité Mixte de Recherche 7059, Centre National de la Recherche Scientifique, Université
Denis Diderot, Paris, France.
Corresponding author: Corinne Leloup, leloup{at}cict.fr .
Abstract
OBJECTIVE Recent data demonstrated that glucose sensing in different tissues is initiated by an intracellular redox signaling pathway
in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the
present study was to determine whether brain glucose hypersensitivity present in obese Zücker rats is related to an alteration
in redox signaling.
RESEARCH DESIGN AND METHODS Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus,
changes in reactive oxygen species levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications
of redox state and mitochondrial functions were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide
dismutase, aconitase activities, and mitochondrial respiration.
RESULTS Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased
insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated
with 1 ) increased reactive oxygen species levels in response to this low glucose load, 2 ) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial
level, and 3 ) overexpression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial
activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced glutathione infusion
in the third ventricle fully reversed the cerebral hypersensitivity to glucose.
CONCLUSIONS The data demonstrated that obese Zücker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an
abnormal redox signaling, which originates from mitochondria dysfunction.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received January 25, 2009.
Accepted June 22, 2009.
© 2009 by the American Diabetes Association.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db09-0110</identifier><identifier>PMID: 19581415</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Aconitate Hydratase - metabolism ; Action Potentials - drug effects ; Animals ; Biological and medical sciences ; Blood glucose test ; Brain - drug effects ; Brain - physiology ; Brain - physiopathology ; Brain research ; Cellular signal transduction ; Complications and side effects ; Diabetes. Impaired glucose tolerance ; Diagnosis ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Glucose ; Glucose - pharmacology ; Health aspects ; Homeostasis ; Hypersensitivity - metabolism ; Hypersensitivity - physiopathology ; Hypothalamus - drug effects ; Hypothalamus - physiology ; Hypothalamus - physiopathology ; Insulin resistance ; Male ; Medical sciences ; Metabolic diseases ; Metabolism ; Metabolites ; Mitochondria - drug effects ; Mitochondria - physiology ; Mitochondrial diseases ; Obesity ; Obesity - genetics ; Obesity - physiopathology ; Original ; Oxidation-Reduction ; Oxidative Phosphorylation - drug effects ; Oxygen Consumption - drug effects ; Physiological aspects ; Physiology ; Rats ; Rats, Zucker ; Research design ; Signal Transduction</subject><ispartof>Diabetes (New York, N.Y.), 2009-10, Vol.58 (10), p.2189-2197</ispartof><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 American Diabetes Association</rights><rights>Copyright American Diabetes Association Oct 2009</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2009 by the American Diabetes Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c678t-1805ff4900ec05bd024f3279a4e05e76b49966a9659daf290aa83b0c660e18a23</citedby><cites>FETCH-LOGICAL-c678t-1805ff4900ec05bd024f3279a4e05e76b49966a9659daf290aa83b0c660e18a23</cites><orcidid>0000-0001-9647-3248 ; 0000-0001-7420-651X ; 0000-0002-7044-2571 ; 0000-0001-7662-1872 ; 0000-0003-2046-0162 ; 0000-0003-2454-5681</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/PMC2750216/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750216/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21998656$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19581415$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00461351$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>COLOMBANI, Anne-Laure</creatorcontrib><creatorcontrib>CARNEIRO, Lionel</creatorcontrib><creatorcontrib>PENICAUD, Luc</creatorcontrib><creatorcontrib>LELOUP, Corinne</creatorcontrib><creatorcontrib>BENANI, Alexandre</creatorcontrib><creatorcontrib>GALINIER, Anne</creatorcontrib><creatorcontrib>JAILLARD, Tristan</creatorcontrib><creatorcontrib>DUPARC, Thibaut</creatorcontrib><creatorcontrib>OFFER, Géraldine</creatorcontrib><creatorcontrib>LORSIGNOL, Anne</creatorcontrib><creatorcontrib>MAGNAN, Christophe</creatorcontrib><creatorcontrib>CASTEILLA, Louis</creatorcontrib><title>Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling
Anne-Laure Colombani 1 ,
Lionel Carneiro 1 ,
Alexandre Benani 1 ,
Anne Galinier 1 ,
Tristan Jaillard 1 ,
Thibaut Duparc 1 ,
Géraldine Offer 1 ,
Anne Lorsignol 1 ,
Christophe Magnan 2 ,
Louis Casteilla 1 ,
Luc Pénicaud 1 and
Corinne Leloup 1
1 Métabolisme, Plasticité et Mitochondrie, Unité Mixte de Recherche 5241, Centre National de la Recherche Scientifique, Université
Paul Sabatier, Toulouse, France;
2 Physiopathologie de la Nutrition, Unité Mixte de Recherche 7059, Centre National de la Recherche Scientifique, Université
Denis Diderot, Paris, France.
Corresponding author: Corinne Leloup, leloup{at}cict.fr .
Abstract
OBJECTIVE Recent data demonstrated that glucose sensing in different tissues is initiated by an intracellular redox signaling pathway
in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the
present study was to determine whether brain glucose hypersensitivity present in obese Zücker rats is related to an alteration
in redox signaling.
RESEARCH DESIGN AND METHODS Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus,
changes in reactive oxygen species levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications
of redox state and mitochondrial functions were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide
dismutase, aconitase activities, and mitochondrial respiration.
RESULTS Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased
insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated
with 1 ) increased reactive oxygen species levels in response to this low glucose load, 2 ) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial
level, and 3 ) overexpression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial
activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced glutathione infusion
in the third ventricle fully reversed the cerebral hypersensitivity to glucose.
CONCLUSIONS The data demonstrated that obese Zücker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an
abnormal redox signaling, which originates from mitochondria dysfunction.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received January 25, 2009.
Accepted June 22, 2009.
© 2009 by the American Diabetes Association.</description><subject>Aconitate Hydratase - metabolism</subject><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood glucose test</subject><subject>Brain - drug effects</subject><subject>Brain - physiology</subject><subject>Brain - physiopathology</subject><subject>Brain research</subject><subject>Cellular signal transduction</subject><subject>Complications and side effects</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diagnosis</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Glucose</subject><subject>Glucose - pharmacology</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Hypersensitivity - metabolism</subject><subject>Hypersensitivity - physiopathology</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - physiology</subject><subject>Hypothalamus - physiopathology</subject><subject>Insulin resistance</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - physiology</subject><subject>Mitochondrial diseases</subject><subject>Obesity</subject><subject>Obesity - genetics</subject><subject>Obesity - physiopathology</subject><subject>Original</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Phosphorylation - drug effects</subject><subject>Oxygen Consumption - drug effects</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Rats</subject><subject>Rats, Zucker</subject><subject>Research design</subject><subject>Signal Transduction</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9klFr2zAUhc3YWLtuD_sDw2xsUJi7K8uWrT0MQuiSQSCwbrA3IcvXjooipZbdNf9-8hLapYShBwn5u0fX95woek3gIqW0-FRXwBMgBJ5Ep4RTntC0-PU0OgUgaUIKXpxEL7y_BgAW1vPohPC8JBnJT6PlpV1Jq7CO59uN61fSyLVW8cwMynmMr9B6bdtY23hZodf99nM8MT12stfOxq6Jv2Pt7uIr3VppAvkyetZI4_HVfj-Lfn69_DGdJ4vl7Nt0skgUK8o-ISXkTZNxAFSQVzWkWROa5jJDyLFgVcY5Y5KznNeySTlIWdIKFGOApJQpPYu-7HQ3Q7XGWqHtO2nEptNr2W2Fk1ocfrF6JVp3K9Iih5SwIHC-E1g9KptPFmK8A8gYoTm5JYH9sH-sczcD-l6stVdojLToBi9YwYqMUh7At4_Aazd0YTJehDfD7xYUAvRuB7XSoNC2caFBNSqKSQo8pRnPR6nkCNWiDbM3zmKjw_UBf3GED6vGYOjRgvODgsD0eNe3cvBelLPF_5rZs8oZgy2K4Ox0eVRbdc77Dpv7CRMQY2TFGFkxRjawb_518oHcZzQA7_eA9Eqapgt51f6eSwnnJctHRz_uHdXt6rfuUNRaVtijfzjk5d8OSMnpHwNJ_RA</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>COLOMBANI, Anne-Laure</creator><creator>CARNEIRO, Lionel</creator><creator>PENICAUD, Luc</creator><creator>LELOUP, Corinne</creator><creator>BENANI, Alexandre</creator><creator>GALINIER, Anne</creator><creator>JAILLARD, Tristan</creator><creator>DUPARC, Thibaut</creator><creator>OFFER, Géraldine</creator><creator>LORSIGNOL, Anne</creator><creator>MAGNAN, Christophe</creator><creator>CASTEILLA, Louis</creator><general>American Diabetes Association</general><scope>IQODW</scope><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>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9647-3248</orcidid><orcidid>https://orcid.org/0000-0001-7420-651X</orcidid><orcidid>https://orcid.org/0000-0002-7044-2571</orcidid><orcidid>https://orcid.org/0000-0001-7662-1872</orcidid><orcidid>https://orcid.org/0000-0003-2046-0162</orcidid><orcidid>https://orcid.org/0000-0003-2454-5681</orcidid></search><sort><creationdate>20091001</creationdate><title>Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling</title><author>COLOMBANI, Anne-Laure ; CARNEIRO, Lionel ; PENICAUD, Luc ; LELOUP, Corinne ; BENANI, Alexandre ; GALINIER, Anne ; JAILLARD, Tristan ; DUPARC, Thibaut ; OFFER, Géraldine ; LORSIGNOL, Anne ; MAGNAN, Christophe ; CASTEILLA, Louis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c678t-1805ff4900ec05bd024f3279a4e05e76b49966a9659daf290aa83b0c660e18a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aconitate Hydratase - metabolism</topic><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood glucose test</topic><topic>Brain - drug effects</topic><topic>Brain - physiology</topic><topic>Brain - physiopathology</topic><topic>Brain research</topic><topic>Cellular signal transduction</topic><topic>Complications and side effects</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diagnosis</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Glucose</topic><topic>Glucose - pharmacology</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Hypersensitivity - metabolism</topic><topic>Hypersensitivity - physiopathology</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - physiology</topic><topic>Hypothalamus - physiopathology</topic><topic>Insulin resistance</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - physiology</topic><topic>Mitochondrial diseases</topic><topic>Obesity</topic><topic>Obesity - genetics</topic><topic>Obesity - physiopathology</topic><topic>Original</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Phosphorylation - drug effects</topic><topic>Oxygen Consumption - drug effects</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Rats</topic><topic>Rats, Zucker</topic><topic>Research design</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>COLOMBANI, Anne-Laure</creatorcontrib><creatorcontrib>CARNEIRO, Lionel</creatorcontrib><creatorcontrib>PENICAUD, Luc</creatorcontrib><creatorcontrib>LELOUP, Corinne</creatorcontrib><creatorcontrib>BENANI, Alexandre</creatorcontrib><creatorcontrib>GALINIER, Anne</creatorcontrib><creatorcontrib>JAILLARD, Tristan</creatorcontrib><creatorcontrib>DUPARC, Thibaut</creatorcontrib><creatorcontrib>OFFER, Géraldine</creatorcontrib><creatorcontrib>LORSIGNOL, Anne</creatorcontrib><creatorcontrib>MAGNAN, Christophe</creatorcontrib><creatorcontrib>CASTEILLA, Louis</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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 Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>COLOMBANI, Anne-Laure</au><au>CARNEIRO, Lionel</au><au>PENICAUD, Luc</au><au>LELOUP, Corinne</au><au>BENANI, Alexandre</au><au>GALINIER, Anne</au><au>JAILLARD, Tristan</au><au>DUPARC, Thibaut</au><au>OFFER, Géraldine</au><au>LORSIGNOL, Anne</au><au>MAGNAN, Christophe</au><au>CASTEILLA, Louis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>58</volume><issue>10</issue><spage>2189</spage><epage>2197</epage><pages>2189-2197</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling
Anne-Laure Colombani 1 ,
Lionel Carneiro 1 ,
Alexandre Benani 1 ,
Anne Galinier 1 ,
Tristan Jaillard 1 ,
Thibaut Duparc 1 ,
Géraldine Offer 1 ,
Anne Lorsignol 1 ,
Christophe Magnan 2 ,
Louis Casteilla 1 ,
Luc Pénicaud 1 and
Corinne Leloup 1
1 Métabolisme, Plasticité et Mitochondrie, Unité Mixte de Recherche 5241, Centre National de la Recherche Scientifique, Université
Paul Sabatier, Toulouse, France;
2 Physiopathologie de la Nutrition, Unité Mixte de Recherche 7059, Centre National de la Recherche Scientifique, Université
Denis Diderot, Paris, France.
Corresponding author: Corinne Leloup, leloup{at}cict.fr .
Abstract
OBJECTIVE Recent data demonstrated that glucose sensing in different tissues is initiated by an intracellular redox signaling pathway
in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the
present study was to determine whether brain glucose hypersensitivity present in obese Zücker rats is related to an alteration
in redox signaling.
RESEARCH DESIGN AND METHODS Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus,
changes in reactive oxygen species levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications
of redox state and mitochondrial functions were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide
dismutase, aconitase activities, and mitochondrial respiration.
RESULTS Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased
insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated
with 1 ) increased reactive oxygen species levels in response to this low glucose load, 2 ) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial
level, and 3 ) overexpression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial
activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced glutathione infusion
in the third ventricle fully reversed the cerebral hypersensitivity to glucose.
CONCLUSIONS The data demonstrated that obese Zücker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an
abnormal redox signaling, which originates from mitochondria dysfunction.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received January 25, 2009.
Accepted June 22, 2009.
© 2009 by the American Diabetes Association.</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>19581415</pmid><doi>10.2337/db09-0110</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9647-3248</orcidid><orcidid>https://orcid.org/0000-0001-7420-651X</orcidid><orcidid>https://orcid.org/0000-0002-7044-2571</orcidid><orcidid>https://orcid.org/0000-0001-7662-1872</orcidid><orcidid>https://orcid.org/0000-0003-2046-0162</orcidid><orcidid>https://orcid.org/0000-0003-2454-5681</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2009-10, Vol.58 (10), p.2189-2197 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_gale_infotracacademiconefile_A209234959 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Aconitate Hydratase - metabolism Action Potentials - drug effects Animals Biological and medical sciences Blood glucose test Brain - drug effects Brain - physiology Brain - physiopathology Brain research Cellular signal transduction Complications and side effects Diabetes. Impaired glucose tolerance Diagnosis Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Glucose Glucose - pharmacology Health aspects Homeostasis Hypersensitivity - metabolism Hypersensitivity - physiopathology Hypothalamus - drug effects Hypothalamus - physiology Hypothalamus - physiopathology Insulin resistance Male Medical sciences Metabolic diseases Metabolism Metabolites Mitochondria - drug effects Mitochondria - physiology Mitochondrial diseases Obesity Obesity - genetics Obesity - physiopathology Original Oxidation-Reduction Oxidative Phosphorylation - drug effects Oxygen Consumption - drug effects Physiological aspects Physiology Rats Rats, Zucker Research design Signal Transduction |
| title | Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling |
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