Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1.
Identifieur interne : 000550 ( Main/Exploration ); précédent : 000549; suivant : 000551Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1.
Auteurs : Ara Koh [Suède] ; Antonio Molinaro [Suède] ; Marcus St Hlman [Suède] ; Muhammad Tanweer Khan [Suède] ; Caroline Schmidt [Suède] ; Louise Manner S-Holm [Suède] ; Hao Wu [Suède] ; Alba Carreras [Suède] ; Heeyoon Jeong [Corée du Sud] ; Louise E. Olofsson [Suède] ; Per-Olof Bergh [Suède] ; Victor Gerdes [Pays-Bas] ; Annick Hartstra [Pays-Bas] ; Maurits De Brauw [Pays-Bas] ; Rosie Perkins [Suède] ; Max Nieuwdorp [Pays-Bas] ; Göran Bergström [Suède] ; Fredrik B Ckhed [Danemark]Source :
- Cell [ 1097-4172 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Cellules HEK293 (MeSH), Cellules cultivées (MeSH), Complexe-1 cible mécanistique de la rapamycine (métabolisme), Diabète de type 2 (microbiologie), Diabète de type 2 (métabolisme), Foie (métabolisme), Histidine (métabolisme), Humains (MeSH), Imidazoles (métabolisme), Insuline (métabolisme), Microbiome gastro-intestinal (MeSH), Mâle (MeSH), Souris (MeSH), Souris de lignée C57BL (MeSH), Séquestosome-1 (métabolisme), Transduction du signal (MeSH), p38 Mitogen-Activated Protein Kinases (métabolisme).
- MESH :
- microbiologie : Diabète de type 2.
- métabolisme : Complexe-1 cible mécanistique de la rapamycine, Diabète de type 2, Foie, Histidine, Imidazoles, Insuline, Séquestosome-1, p38 Mitogen-Activated Protein Kinases.
- Animaux, Cellules HEK293, Cellules cultivées, Humains, Microbiome gastro-intestinal, Mâle, Souris, Souris de lignée C57BL, Transduction du signal.
English descriptors
- KwdEn :
- Animals (MeSH), Cells, Cultured (MeSH), Diabetes Mellitus, Type 2 (metabolism), Diabetes Mellitus, Type 2 (microbiology), Gastrointestinal Microbiome (MeSH), HEK293 Cells (MeSH), Histidine (metabolism), Humans (MeSH), Imidazoles (metabolism), Insulin (metabolism), Liver (metabolism), Male (MeSH), Mechanistic Target of Rapamycin Complex 1 (metabolism), Mice (MeSH), Mice, Inbred C57BL (MeSH), Sequestosome-1 Protein (metabolism), Signal Transduction (MeSH), p38 Mitogen-Activated Protein Kinases (metabolism).
- MESH :
- chemical , metabolism : Histidine, Imidazoles, Insulin, Mechanistic Target of Rapamycin Complex 1, Sequestosome-1 Protein, p38 Mitogen-Activated Protein Kinases.
- metabolism : Diabetes Mellitus, Type 2, Liver.
- microbiology : Diabetes Mellitus, Type 2.
- Animals, Cells, Cultured, Gastrointestinal Microbiome, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Signal Transduction.
Abstract
Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
DOI: 10.1016/j.cell.2018.09.055
PubMed: 30401435
Affiliations:
- Corée du Sud, Danemark, Pays-Bas, Suède
- Hollande-Septentrionale, Hovedstaden
- Amsterdam, Copenhague
- Université d'Amsterdam
Links toward previous steps (curation, corpus...)
Le document en format XML
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Department of Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Manner S Holm, Louise" sort="Manner S Holm, Louise" uniqKey="Manner S Holm L" first="Louise" last="Manner S-Holm">Louise Manner S-Holm</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Carreras, Alba" sort="Carreras, Alba" uniqKey="Carreras A" first="Alba" last="Carreras">Alba Carreras</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Jeong, Heeyoon" sort="Jeong, Heeyoon" uniqKey="Jeong H" first="Heeyoon" last="Jeong">Heeyoon Jeong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673</wicri:regionArea><wicri:noRegion>Pohang 37673</wicri:noRegion></affiliation></author><author><name sortKey="Olofsson, Louise E" sort="Olofsson, Louise E" uniqKey="Olofsson L" first="Louise E" last="Olofsson">Louise E. Olofsson</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Bergh, Per Olof" sort="Bergh, Per Olof" uniqKey="Bergh P" first="Per-Olof" last="Bergh">Per-Olof Bergh</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Gerdes, Victor" sort="Gerdes, Victor" uniqKey="Gerdes V" first="Victor" last="Gerdes">Victor Gerdes</name><affiliation wicri:level="3"><nlm:affiliation>Slotervaart Hospital, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Slotervaart Hospital, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Hartstra, Annick" sort="Hartstra, Annick" uniqKey="Hartstra A" first="Annick" last="Hartstra">Annick Hartstra</name><affiliation wicri:level="4"><nlm:affiliation>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName><orgName type="university">Université d'Amsterdam</orgName></affiliation></author><author><name sortKey="De Brauw, Maurits" sort="De Brauw, Maurits" uniqKey="De Brauw M" first="Maurits" last="De Brauw">Maurits De Brauw</name><affiliation wicri:level="3"><nlm:affiliation>Slotervaart Hospital, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Slotervaart Hospital, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Perkins, Rosie" sort="Perkins, Rosie" uniqKey="Perkins R" first="Rosie" last="Perkins">Rosie Perkins</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Nieuwdorp, Max" sort="Nieuwdorp, Max" uniqKey="Nieuwdorp M" first="Max" last="Nieuwdorp">Max Nieuwdorp</name><affiliation wicri:level="3"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; VU University Medical Center, Free University Amsterdam, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; VU University Medical Center, Free University Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Bergstrom, Goran" sort="Bergstrom, Goran" uniqKey="Bergstrom G" first="Göran" last="Bergström">Göran Bergström</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="B Ckhed, Fredrik" sort="B Ckhed, Fredrik" uniqKey="B Ckhed F" first="Fredrik" last="B Ckhed">Fredrik B Ckhed</name><affiliation wicri:level="3"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: fredrik@wlab.gu.se.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen</wicri:regionArea><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:30401435</idno><idno type="pmid">30401435</idno><idno type="doi">10.1016/j.cell.2018.09.055</idno><idno type="wicri:Area/Main/Corpus">000411</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000411</idno><idno type="wicri:Area/Main/Curation">000411</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000411</idno><idno type="wicri:Area/Main/Exploration">000411</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1.</title><author><name sortKey="Koh, Ara" sort="Koh, Ara" uniqKey="Koh A" first="Ara" last="Koh">Ara Koh</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Molinaro, Antonio" sort="Molinaro, Antonio" uniqKey="Molinaro A" first="Antonio" last="Molinaro">Antonio Molinaro</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="St Hlman, Marcus" sort="St Hlman, Marcus" uniqKey="St Hlman M" first="Marcus" last="St Hlman">Marcus St Hlman</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Khan, Muhammad Tanweer" sort="Khan, Muhammad Tanweer" uniqKey="Khan M" first="Muhammad Tanweer" last="Khan">Muhammad Tanweer Khan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Schmidt, Caroline" sort="Schmidt, Caroline" uniqKey="Schmidt C" first="Caroline" last="Schmidt">Caroline Schmidt</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Manner S Holm, Louise" sort="Manner S Holm, Louise" uniqKey="Manner S Holm L" first="Louise" last="Manner S-Holm">Louise Manner S-Holm</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Carreras, Alba" sort="Carreras, Alba" uniqKey="Carreras A" first="Alba" last="Carreras">Alba Carreras</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Jeong, Heeyoon" sort="Jeong, Heeyoon" uniqKey="Jeong H" first="Heeyoon" last="Jeong">Heeyoon Jeong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673</wicri:regionArea><wicri:noRegion>Pohang 37673</wicri:noRegion></affiliation></author><author><name sortKey="Olofsson, Louise E" sort="Olofsson, Louise E" uniqKey="Olofsson L" first="Louise E" last="Olofsson">Louise E. Olofsson</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Bergh, Per Olof" sort="Bergh, Per Olof" uniqKey="Bergh P" first="Per-Olof" last="Bergh">Per-Olof Bergh</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Gerdes, Victor" sort="Gerdes, Victor" uniqKey="Gerdes V" first="Victor" last="Gerdes">Victor Gerdes</name><affiliation wicri:level="3"><nlm:affiliation>Slotervaart Hospital, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Slotervaart Hospital, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Hartstra, Annick" sort="Hartstra, Annick" uniqKey="Hartstra A" first="Annick" last="Hartstra">Annick Hartstra</name><affiliation wicri:level="4"><nlm:affiliation>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName><orgName type="university">Université d'Amsterdam</orgName></affiliation></author><author><name sortKey="De Brauw, Maurits" sort="De Brauw, Maurits" uniqKey="De Brauw M" first="Maurits" last="De Brauw">Maurits De Brauw</name><affiliation wicri:level="3"><nlm:affiliation>Slotervaart Hospital, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Slotervaart Hospital, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Perkins, Rosie" sort="Perkins, Rosie" uniqKey="Perkins R" first="Rosie" last="Perkins">Rosie Perkins</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="Nieuwdorp, Max" sort="Nieuwdorp, Max" uniqKey="Nieuwdorp M" first="Max" last="Nieuwdorp">Max Nieuwdorp</name><affiliation wicri:level="3"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; VU University Medical Center, Free University Amsterdam, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; VU University Medical Center, Free University Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Bergstrom, Goran" sort="Bergstrom, Goran" uniqKey="Bergstrom G" first="Göran" last="Bergström">Göran Bergström</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg</wicri:regionArea><wicri:noRegion>Gothenburg</wicri:noRegion></affiliation></author><author><name sortKey="B Ckhed, Fredrik" sort="B Ckhed, Fredrik" uniqKey="B Ckhed F" first="Fredrik" last="B Ckhed">Fredrik B Ckhed</name><affiliation wicri:level="3"><nlm:affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: fredrik@wlab.gu.se.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen</wicri:regionArea><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author></analytic><series><title level="j">Cell</title><idno type="eISSN">1097-4172</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Cells, Cultured (MeSH)</term><term>Diabetes Mellitus, Type 2 (metabolism)</term><term>Diabetes Mellitus, Type 2 (microbiology)</term><term>Gastrointestinal Microbiome (MeSH)</term><term>HEK293 Cells (MeSH)</term><term>Histidine (metabolism)</term><term>Humans (MeSH)</term><term>Imidazoles (metabolism)</term><term>Insulin (metabolism)</term><term>Liver (metabolism)</term><term>Male (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Sequestosome-1 Protein (metabolism)</term><term>Signal Transduction (MeSH)</term><term>p38 Mitogen-Activated Protein Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cellules HEK293 (MeSH)</term><term>Cellules cultivées (MeSH)</term><term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term><term>Diabète de type 2 (microbiologie)</term><term>Diabète de type 2 (métabolisme)</term><term>Foie (métabolisme)</term><term>Histidine (métabolisme)</term><term>Humains (MeSH)</term><term>Imidazoles (métabolisme)</term><term>Insuline (métabolisme)</term><term>Microbiome gastro-intestinal (MeSH)</term><term>Mâle (MeSH)</term><term>Souris (MeSH)</term><term>Souris de lignée C57BL (MeSH)</term><term>Séquestosome-1 (métabolisme)</term><term>Transduction du signal (MeSH)</term><term>p38 Mitogen-Activated Protein Kinases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Histidine</term><term>Imidazoles</term><term>Insulin</term><term>Mechanistic Target of Rapamycin Complex 1</term><term>Sequestosome-1 Protein</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Diabetes Mellitus, Type 2</term><term>Liver</term></keywords><keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Diabète de type 2</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Diabetes Mellitus, Type 2</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term><term>Diabète de type 2</term><term>Foie</term><term>Histidine</term><term>Imidazoles</term><term>Insuline</term><term>Séquestosome-1</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Gastrointestinal Microbiome</term><term>HEK293 Cells</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules cultivées</term><term>Humains</term><term>Microbiome gastro-intestinal</term><term>Mâle</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30401435</PMID><DateCompleted><Year>2019</Year><Month>07</Month><Day>29</Day></DateCompleted><DateRevised><Year>2019</Year><Month>07</Month><Day>29</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-4172</ISSN><JournalIssue CitedMedium="Internet"><Volume>175</Volume><Issue>4</Issue><PubDate><Year>2018</Year><Month>11</Month><Day>01</Day></PubDate></JournalIssue><Title>Cell</Title><ISOAbbreviation>Cell</ISOAbbreviation></Journal><ArticleTitle>Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1.</ArticleTitle><Pagination><MedlinePgn>947-961.e17</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0092-8674(18)31306-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.cell.2018.09.055</ELocationID><Abstract><AbstractText>Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.</AbstractText><CopyrightInformation>Copyright © 2018 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Koh</LastName><ForeName>Ara</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Molinaro</LastName><ForeName>Antonio</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ståhlman</LastName><ForeName>Marcus</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khan</LastName><ForeName>Muhammad Tanweer</ForeName><Initials>MT</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmidt</LastName><ForeName>Caroline</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mannerås-Holm</LastName><ForeName>Louise</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Hao</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carreras</LastName><ForeName>Alba</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeong</LastName><ForeName>Heeyoon</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Olofsson</LastName><ForeName>Louise E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bergh</LastName><ForeName>Per-Olof</ForeName><Initials>PO</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gerdes</LastName><ForeName>Victor</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Slotervaart Hospital, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hartstra</LastName><ForeName>Annick</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Brauw</LastName><ForeName>Maurits</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Slotervaart Hospital, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perkins</LastName><ForeName>Rosie</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nieuwdorp</LastName><ForeName>Max</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; VU University Medical Center, Free University Amsterdam, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bergström</LastName><ForeName>Göran</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bäckhed</LastName><ForeName>Fredrik</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: fredrik@wlab.gu.se.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>10</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell</MedlineTA><NlmUniqueID>0413066</NlmUniqueID><ISSNLinking>0092-8674</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007328">Insulin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000071456">Sequestosome-1 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>1074-59-5</RegistryNumber><NameOfSubstance UI="C018976">5-imidazolepropionic acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QD397987E</RegistryNumber><NameOfSubstance UI="D006639">Histidine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.24</RegistryNumber><NameOfSubstance UI="D048051">p38 Mitogen-Activated Protein Kinases</NameOfSubstance></Chemical></ChemicalList><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Nat Rev Endocrinol. 2018 Dec;15(1):3</RefSource><PMID Version="1">30410100</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003924" MajorTopicYN="N">Diabetes Mellitus, Type 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000069196" MajorTopicYN="Y">Gastrointestinal Microbiome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006639" MajorTopicYN="N">Histidine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007093" MajorTopicYN="N">Imidazoles</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007328" MajorTopicYN="N">Insulin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000071456" MajorTopicYN="N">Sequestosome-1 Protein</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="Y">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D048051" MajorTopicYN="N">p38 Mitogen-Activated Protein Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">IRS</Keyword><Keyword MajorTopicYN="Y">histidine</Keyword><Keyword MajorTopicYN="Y">imidazole propionate</Keyword><Keyword MajorTopicYN="Y">mTORC1</Keyword><Keyword MajorTopicYN="Y">microbiome</Keyword><Keyword MajorTopicYN="Y">p38γ</Keyword><Keyword MajorTopicYN="Y">p62</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>03</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>06</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>09</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>11</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>11</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>7</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30401435</ArticleId><ArticleId IdType="pii">S0092-8674(18)31306-0</ArticleId><ArticleId IdType="doi">10.1016/j.cell.2018.09.055</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Corée du Sud</li><li>Danemark</li><li>Pays-Bas</li><li>Suède</li></country><region><li>Hollande-Septentrionale</li><li>Hovedstaden</li></region><settlement><li>Amsterdam</li><li>Copenhague</li></settlement><orgName><li>Université d'Amsterdam</li></orgName></list><tree><country name="Suède"><noRegion><name sortKey="Koh, Ara" sort="Koh, Ara" uniqKey="Koh A" first="Ara" last="Koh">Ara Koh</name></noRegion><name sortKey="Bergh, Per Olof" sort="Bergh, Per Olof" uniqKey="Bergh P" first="Per-Olof" last="Bergh">Per-Olof Bergh</name><name sortKey="Bergstrom, Goran" sort="Bergstrom, Goran" uniqKey="Bergstrom G" first="Göran" last="Bergström">Göran Bergström</name><name sortKey="Carreras, Alba" sort="Carreras, Alba" uniqKey="Carreras A" first="Alba" last="Carreras">Alba Carreras</name><name sortKey="Khan, Muhammad Tanweer" sort="Khan, Muhammad Tanweer" uniqKey="Khan M" first="Muhammad Tanweer" last="Khan">Muhammad Tanweer Khan</name><name sortKey="Manner S Holm, Louise" sort="Manner S Holm, Louise" uniqKey="Manner S Holm L" first="Louise" last="Manner S-Holm">Louise Manner S-Holm</name><name sortKey="Molinaro, Antonio" sort="Molinaro, Antonio" uniqKey="Molinaro A" first="Antonio" last="Molinaro">Antonio Molinaro</name><name sortKey="Olofsson, Louise E" sort="Olofsson, Louise E" uniqKey="Olofsson L" first="Louise E" last="Olofsson">Louise E. Olofsson</name><name sortKey="Perkins, Rosie" sort="Perkins, Rosie" uniqKey="Perkins R" first="Rosie" last="Perkins">Rosie Perkins</name><name sortKey="Schmidt, Caroline" sort="Schmidt, Caroline" uniqKey="Schmidt C" first="Caroline" last="Schmidt">Caroline Schmidt</name><name sortKey="St Hlman, Marcus" sort="St Hlman, Marcus" uniqKey="St Hlman M" first="Marcus" last="St Hlman">Marcus St Hlman</name><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name></country><country name="Corée du Sud"><noRegion><name sortKey="Jeong, Heeyoon" sort="Jeong, Heeyoon" uniqKey="Jeong H" first="Heeyoon" last="Jeong">Heeyoon Jeong</name></noRegion></country><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Gerdes, Victor" sort="Gerdes, Victor" uniqKey="Gerdes V" first="Victor" last="Gerdes">Victor Gerdes</name></region><name sortKey="De Brauw, Maurits" sort="De Brauw, Maurits" uniqKey="De Brauw M" first="Maurits" last="De Brauw">Maurits De Brauw</name><name sortKey="Hartstra, Annick" sort="Hartstra, Annick" uniqKey="Hartstra A" first="Annick" last="Hartstra">Annick Hartstra</name><name sortKey="Nieuwdorp, Max" sort="Nieuwdorp, Max" uniqKey="Nieuwdorp M" first="Max" last="Nieuwdorp">Max Nieuwdorp</name></country><country name="Danemark"><region name="Hovedstaden"><name sortKey="B Ckhed, Fredrik" sort="B Ckhed, Fredrik" uniqKey="B Ckhed F" first="Fredrik" last="B Ckhed">Fredrik B Ckhed</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|clé= pubmed:30401435
|texte= Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1.
}}
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| NlmPubMed2Wicri -a RapamycinFungusV1
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