title: Evidence connecting old, new and neglected glucose-lowering drugs to bile acid-induced GLP-1 secretion: A review.
abstract: Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G-protein-coupled receptor 5 and the nuclear farnesoid X receptor, in intestinal L cells. The present article critically reviews current evidence connecting established glucose-lowering drugs to bile acid-induced GLP-1 secretion, and discusses whether bile acid-induced GLP-1 secretion may constitute a new basis for understanding how metformin, inhibitors of the apical sodium-dependent bile acids transporter, and bile acid sequestrants - old, new and neglected glucose-lowering drugs - improve glucose metabolism.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Kårhus
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brønden
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: David P
authors.initials: DP
authors.lastname: Sonne
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.|Steno Diabetes Center, Copenhagen, University of Copenhagen, Gentofte, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, The Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fillip K
authors.identifier: 0000-0002-2495-5034
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism; D019317:Evidence-Based Medicine; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008954:Models, Biological
chemical_list: D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1
keywords: 
  GLP-1; ASBT inhibitors, bile acid, bile acid sequestrants, drug mechanism; antidiabetic drug; incretin therapy; metformin; type 2 diabetes