title: Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion.
abstract: To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide, glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake.
  
  
  
  On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled.
  
  
  
  In both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP-1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C-peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups.
  
  
  
  CDCA increased GLP-1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid-induced activation of TGR5 on L cells increases GLP-1 secretion, which, in turn, may result in amplification of glucose-stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP-1 secretion in humans.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University Copenhagen, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Hansen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University Copenhagen, Hellerup, Denmark.|Department of Endocrinology and Metabolism, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Scheltema
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University Copenhagen, Copenhagen, Denmark.
authors.forename: D P
authors.initials: DP
authors.lastname: Sonne
authors.affiliation: Department of Clinical Biochemistry, University Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Hansen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University Copenhagen, Hellerup, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Sperling
authors.affiliation: Department of Clinical Biochemistry, University Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: J F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University Copenhagen, Hellerup, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University Copenhagen, Copenhagen, Denmark.
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000368:Aged; D001647:Bile Acids and Salts / Q000037:antagonists & inhibitors / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D000069472:Colesevelam Hydrochloride / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010919:Placebos
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D002096:C-Peptide; D054795:Incretins; D007328:Insulin; D010919:Placebos; D002635:Chenodeoxycholic Acid; D052216:Glucagon-Like Peptide 1; D000069472:Colesevelam Hydrochloride
keywords: GLP-1; antidiabetic drug; drug development; glucose metabolism; type 2 diabetes