OcrV1, Main, Exploration, bibRecord, 000A84

Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration

Identifieur interne : 000A84 ( Main/Exploration ); précédent : 000A83; suivant : 000A85

Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration

Auteurs : I. R. Sweet [États-Unis] ; M. Gilbert [États-Unis] ; E. Maloney [États-Unis] ; D. M. Hockenbery [États-Unis] ; M. W. Schwartz [États-Unis] ; F. Kim [États-Unis]

Source :

Diabetologia : (Berlin) [ 0012-186X ] ; 2009.

RBID : Pascal:09-0186253

Descripteurs français

Pascal (Inist)
- Endothélium, Inflammation, Glucose, Mitochondrie, Respiration, Microcirculation, Diabète, Cellule endothéliale, Hyperglycémie, Lactate, Stress, Facteur transcription NFκB, Consommation oxygène, Homme.
Wicri :
- topic : Glucose, Diabète, Homme.

English descriptors

KwdEn :
- Diabetes mellitus, Endothelial cell, Endothelium, Glucose, Human, Hyperglycemia, Inflammation, Lactates, Microcirculation, Mitochondria, Oxygen consumption, Respiration, Stress, Transcription factor NFκB.

Abstract

Aims/hypothesis Exposure of endothelial cells to high glucose levels suppresses responses to insulin, including induction of endothelial nitric oxide synthase activity, through pro-inflammatory signalling via the inhibitor of nuclear factor kappaB (IκB)α-nuclear factor kappaB (NF-κB) pathway. In the current study, we aimed to identify metabolic responses to glucose excess that mediate endothelial cell inflammation and insulin resistance. Since endothelial cells decrease their oxygen consumption rate (OCR) in response to glucose, we hypothesised that increased mitochondrial function would not mediate these cells' response to excess substrate. Methods The effects of glycolytic and mitochondrial fuels on metabolic intermediates and end-products of glycolytic and oxidative metabolism, including glucose 6-phosphate (G6P), lactate, CO₂, NAD(P)H and OCR, were measured in cultured human microvascular endothelial cells and correlated with IκBα phosphorylation. Results In response to increases in glucose concentration from low to physiological levels (0-5 mmol/l), production of G6P, lactate, NAD(P)H and CO₂ each increased as expected, while OCR was sharply reduced. IκBα activation was detected at glucose concentrations >5 mmol/l, which was associated with parallel increases of G6P levels, whereas downstream metabolic pathways were insensitive to excess substrate. Conclusions/interpretation Phosphorylation of IκBα by excess glucose correlates with increased levels of the glycolytic intermediate G6P, but not with lactate generation or OCR, which are inhibited well below saturation levels at physiological glucose concentrations. These findings suggest that oxidative stress due to increased mitochondrial respiration is unlikely to mediate endothelial inflammation induced by excess glucose and suggests instead the involvement of G6P accumulation in the adverse effects of hyperglycaemia on endothelial cells.

Affiliations:

Links toward previous steps (curation, corpus...)

to stream PascalFrancis, to step Corpus: 000230
to stream PascalFrancis, to step Curation: 000549
to stream PascalFrancis, to step Checkpoint: 000200
to stream Main, to step Merge: 000A94
to stream Main, to step Curation: 000A84

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration</title>
<author><name sortKey="Sweet, I R" sort="Sweet, I R" uniqKey="Sweet I" first="I. R." last="Sweet">I. R. Sweet</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gilbert, M" sort="Gilbert, M" uniqKey="Gilbert M" first="M." last="Gilbert">M. Gilbert</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maloney, E" sort="Maloney, E" uniqKey="Maloney E" first="E." last="Maloney">E. Maloney</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hockenbery, D M" sort="Hockenbery, D M" uniqKey="Hockenbery D" first="D. M." last="Hockenbery">D. M. Hockenbery</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Division of Clinical Research, Fred Hutchinson Cancer Research Center</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schwartz, M W" sort="Schwartz, M W" uniqKey="Schwartz M" first="M. W." last="Schwartz">M. W. Schwartz</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, F" sort="Kim, F" uniqKey="Kim F" first="F." last="Kim">F. Kim</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">09-0186253</idno>
<date when="2009">2009</date>
<idno type="stanalyst">PASCAL 09-0186253 INIST</idno>
<idno type="RBID">Pascal:09-0186253</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000230</idno>
<idno type="wicri:Area/PascalFrancis/Curation">000549</idno>
<idno type="wicri:Area/PascalFrancis/Checkpoint">000200</idno>
<idno type="wicri:doubleKey">0012-186X:2009:Sweet I:endothelial:inflammation:induced</idno>
<idno type="wicri:Area/Main/Merge">000A94</idno>
<idno type="wicri:Area/Main/Curation">000A84</idno>
<idno type="wicri:Area/Main/Exploration">000A84</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration</title>
<author><name sortKey="Sweet, I R" sort="Sweet, I R" uniqKey="Sweet I" first="I. R." last="Sweet">I. R. Sweet</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gilbert, M" sort="Gilbert, M" uniqKey="Gilbert M" first="M." last="Gilbert">M. Gilbert</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maloney, E" sort="Maloney, E" uniqKey="Maloney E" first="E." last="Maloney">E. Maloney</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hockenbery, D M" sort="Hockenbery, D M" uniqKey="Hockenbery D" first="D. M." last="Hockenbery">D. M. Hockenbery</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Division of Clinical Research, Fred Hutchinson Cancer Research Center</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schwartz, M W" sort="Schwartz, M W" uniqKey="Schwartz M" first="M. W." last="Schwartz">M. W. Schwartz</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, F" sort="Kim, F" uniqKey="Kim F" first="F." last="Kim">F. Kim</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, 815 Mercer Street, Box 358055</s1>
<s2>Seattle, Washington 98195-8055</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle, Washington 98195-8055</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Diabetologia : (Berlin)</title>
<title level="j" type="abbreviated">Diabetologia : (Berl.)</title>
<idno type="ISSN">0012-186X</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Diabetologia : (Berlin)</title>
<title level="j" type="abbreviated">Diabetologia : (Berl.)</title>
<idno type="ISSN">0012-186X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Diabetes mellitus</term>
<term>Endothelial cell</term>
<term>Endothelium</term>
<term>Glucose</term>
<term>Human</term>
<term>Hyperglycemia</term>
<term>Inflammation</term>
<term>Lactates</term>
<term>Microcirculation</term>
<term>Mitochondria</term>
<term>Oxygen consumption</term>
<term>Respiration</term>
<term>Stress</term>
<term>Transcription factor NFκB</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Endothélium</term>
<term>Inflammation</term>
<term>Glucose</term>
<term>Mitochondrie</term>
<term>Respiration</term>
<term>Microcirculation</term>
<term>Diabète</term>
<term>Cellule endothéliale</term>
<term>Hyperglycémie</term>
<term>Lactate</term>
<term>Stress</term>
<term>Facteur transcription NFκB</term>
<term>Consommation oxygène</term>
<term>Homme</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Glucose</term>
<term>Diabète</term>
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Aims/hypothesis Exposure of endothelial cells to high glucose levels suppresses responses to insulin, including induction of endothelial nitric oxide synthase activity, through pro-inflammatory signalling via the inhibitor of nuclear factor kappaB (IκB)α-nuclear factor kappaB (NF-κB) pathway. In the current study, we aimed to identify metabolic responses to glucose excess that mediate endothelial cell inflammation and insulin resistance. Since endothelial cells decrease their oxygen consumption rate (OCR) in response to glucose, we hypothesised that increased mitochondrial function would not mediate these cells' response to excess substrate. Methods The effects of glycolytic and mitochondrial fuels on metabolic intermediates and end-products of glycolytic and oxidative metabolism, including glucose 6-phosphate (G6P), lactate, CO<sub>2</sub>
, NAD(P)H and OCR, were measured in cultured human microvascular endothelial cells and correlated with IκBα phosphorylation. Results In response to increases in glucose concentration from low to physiological levels (0-5 mmol/l), production of G6P, lactate, NAD(P)H and CO<sub>2</sub>
 each increased as expected, while OCR was sharply reduced. IκBα activation was detected at glucose concentrations >5 mmol/l, which was associated with parallel increases of G6P levels, whereas downstream metabolic pathways were insensitive to excess substrate. Conclusions/interpretation Phosphorylation of IκBα by excess glucose correlates with increased levels of the glycolytic intermediate G6P, but not with lactate generation or OCR, which are inhibited well below saturation levels at physiological glucose concentrations. These findings suggest that oxidative stress due to increased mitochondrial respiration is unlikely to mediate endothelial inflammation induced by excess glucose and suggests instead the involvement of G6P accumulation in the adverse effects of hyperglycaemia on endothelial cells.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Washington (État)</li>
</region>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Sweet, I R" sort="Sweet, I R" uniqKey="Sweet I" first="I. R." last="Sweet">I. R. Sweet</name>
</noRegion>
<name sortKey="Gilbert, M" sort="Gilbert, M" uniqKey="Gilbert M" first="M." last="Gilbert">M. Gilbert</name>
<name sortKey="Hockenbery, D M" sort="Hockenbery, D M" uniqKey="Hockenbery D" first="D. M." last="Hockenbery">D. M. Hockenbery</name>
<name sortKey="Kim, F" sort="Kim, F" uniqKey="Kim F" first="F." last="Kim">F. Kim</name>
<name sortKey="Maloney, E" sort="Maloney, E" uniqKey="Maloney E" first="E." last="Maloney">E. Maloney</name>
<name sortKey="Schwartz, M W" sort="Schwartz, M W" uniqKey="Schwartz M" first="M. W." last="Schwartz">M. W. Schwartz</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Ticri/CIDE/explor/OcrV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A84 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000A84 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Ticri/CIDE
   |area=    OcrV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     Pascal:09-0186253
   |texte=   Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration
}}

This area was generated with Dilib version V0.6.32.
Data generation: Sat Nov 11 16:53:45 2017. Site generation: Mon Mar 11 23:15:16 2024

	Serveur d'exploration sur l'OCR
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur l'OCR

Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration

Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri