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Farnesoid X recepto...
Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells
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Trabelsi, M. S. (author)
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Daoudi, M. (author)
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Prawitt, J. (author)
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show more...
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Ducastel, S. (author)
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Touche, V. (author)
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- Sayin, Sama I. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Perino, A. (author)
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Brighton, C. A. (author)
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Sebti, Y. (author)
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Kluza, J. (author)
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Briand, O. (author)
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Dehondt, H. (author)
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Vallez, E. (author)
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Dorchies, E. (author)
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Baud, G. (author)
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Spinelli, V. (author)
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Hennuyer, N. (author)
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Caron, S. (author)
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Bantubungi, K. (author)
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Caiazzo, R. (author)
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Reimann, F. (author)
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Marchetti, P. (author)
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Lefebvre, P. (author)
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- Bäckhed, Fredrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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Gribble, F. M. (author)
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Schoonjans, K. (author)
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Pattou, F. (author)
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Tailleux, A. (author)
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Staels, B. (author)
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Lestavel, S. (author)
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(creator_code:org_t)
- 2015-07-02
- 2015
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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https://www.nature.c...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and the nuclear receptor FXR. BA sequestrants (BAS) complex bile acids in the intestinal lumen and decrease intestinal FXR activity. The BAS-BA complex also induces glucagon-like peptide-1 (GLP-1) production by L cells which potentiates beta-cell glucose-induced insulin secretion. Whether FXR is expressed in L cells and controls GLP-1 production is unknown. Here, we show that FXR activation in L cells decreases proglucagon expression by interfering with the glucose-responsive factor Carbohydrate-Responsive Element Binding Protein (ChREBP) and GLP-1 secretion by inhibiting glycolysis. In vivo, FXR deficiency increases GLP-1 gene expression and secretion in response to glucose hence improving glucose metabolism. Moreover, treatment of ob/ob mice with the BAS colesevelam increases intestinal proglucagon gene expression and improves glycaemia in a FXR-dependent manner. These findings identify the FXR/GLP-1 pathway as a new mechanism of BA control of glucose metabolism and a pharmacological target for type 2 diabetes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- TYPE-2 DIABETES-MELLITUS
- BILE-ACID RECEPTORS
- RAT SMALL-INTESTINE
- GLUCOSE-HOMEOSTASIS
- GLP-1 SECRETION
- METABOLIC-RATE
- FXR
- MICE
- OBESITY
- EXPRESSION
- Multidisciplinary Sciences
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Trabelsi, M. S.
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Daoudi, M.
-
Prawitt, J.
-
Ducastel, S.
-
Touche, V.
-
Sayin, Sama I.
-
show more...
-
Perino, A.
-
Brighton, C. A.
-
Sebti, Y.
-
Kluza, J.
-
Briand, O.
-
Dehondt, H.
-
Vallez, E.
-
Dorchies, E.
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Baud, G.
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Spinelli, V.
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Hennuyer, N.
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Caron, S.
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Bantubungi, K.
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Caiazzo, R.
-
Reimann, F.
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Marchetti, P.
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Lefebvre, P.
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Bäckhed, Fredrik ...
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Gribble, F. M.
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Schoonjans, K.
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Pattou, F.
-
Tailleux, A.
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Staels, B.
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Lestavel, S.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature Communica ...
- By the university
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University of Gothenburg