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Microbially Produce...
Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1
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- Koh, Ara (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Molinaro, Antonio (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Ståhlman, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Khan, Muhammad Tanweer (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Schmidt, Caroline, 1966 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Mannerås Holm, Louise, 1980 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Wu, Hao (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Carreras, Alba (author)
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- Olofsson, Louise, 1977 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bergh, Per-Olof (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Gerdes, V. (author)
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Hartstra, A. (author)
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de Brauw, M. (author)
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- Perkins, Rosie, 1965 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Nieuwdorp, Max (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bergström, Göran, 1964 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bäckhed, Fredrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: Cell. - : Elsevier BV. - 0092-8674. ; 175:4
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 p38 gamma 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- gut microbiota
- receptor substrate-1
- serum metabolome
- amino-acids
- protein
- pathway
- obesity
- activation
- autophosphorylation
- disease
- Biochemistry & Molecular Biology
- Cell Biology
- iences
- v66
- p1218
- hroder i
- 1991
- journal of biological chemistry
- v266
- p13572
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cell
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- By the author/editor
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Koh, Ara
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Molinaro, Antoni ...
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Ståhlman, Marcus ...
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Khan, Muhammad T ...
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Schmidt, Carolin ...
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Mannerås Holm, L ...
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Wu, Hao
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Carreras, Alba
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Olofsson, Louise ...
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Bergh, Per-Olof
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Gerdes, V.
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Hartstra, A.
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de Brauw, M.
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Perkins, Rosie, ...
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Nieuwdorp, Max
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Bergström, Göran ...
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Bäckhed, Fredrik ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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Cell
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University of Gothenburg