title: Glucose-lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization.
abstract: Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling molecules via receptors, including the G protein-coupled receptor TGR5 and the nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA sequestration, which interrupts the entero-hepatic circulation of BAs, constitutes a plausible action mechanism of BA sequestrants. An increase of intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation is the most commonly proposed mechanism, but recent studies also argue for a direct entero-hepatic action to enhance glucose utilization. We discuss here recent findings on the mechanisms of sequestrant-mediated glucose lowering via an increase of splanchnic glucose utilization through entero-hepatic FXR signaling.
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France; Université Lille 2, 59000 Lille, France; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1011, 59000 Lille, France; Institut Pasteur de Lille, 59000 Lille, France.
authors.forename: Janne
authors.initials: J
authors.lastname: Prawitt
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France; Université Lille 2, 59000 Lille, France; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1011, 59000 Lille, France; Institut Pasteur de Lille, 59000 Lille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caron
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France; Université Lille 2, 59000 Lille, France; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1011, 59000 Lille, France; Institut Pasteur de Lille, 59000 Lille, France. Electronic address: bart.staels@pasteur-lille.fr.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: FXR; TGR5; bile acid sequestrant; glucose homeostasis; type 2 diabetes