title: Effects of chenodeoxycholic acid on the secretion of gut peptides and fibroblast growth factors in healthy humans.
abstract: BACKGROUND
  Recent evidence suggests bile acids (BAs) are involved in the glycemic control via TGR5 activation with the subsequent release of gut peptides and farnesoid X receptor activation with ensuing release of fibroblast growth factors (FGFs).
  
  
  OBJECTIVE
  We hypothesized that intraduodenal infusions of chenodeoxycholic acid (CDCA) would stimulate FGF and gut peptide secretion, thereby positively influencing glucose homeostasis.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled, crossover trial included 12 healthy volunteers who received intraduodenal infusions (2.0 mL/min for 180 minutes) of saline, CDCA (5 or 15 mmol/L), and a fatty acid (sodium oleate), either alone or with 5 mmol/L CDCA. After 60 minutes, an oral glucose tolerance test (oGTT) was performed.
  
  
  METHODS
  Plasma levels of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine, cholecystokinin (CCK), total BAs, FGF19, FGF21, C-peptide, insulin, glucose, and glucagon were measured.
  
  
  RESULTS
  Within the first 60 minutes, high-concentration CDCA induced a small but significant increase in GLP-1 and CCK secretion (P = .016 and P =.011), whereas plasma C-peptide, insulin, and glucose were not affected. Attenuated C-peptide and insulin release was observed after the oGTT with 15 mmol/L CDCA (P = .013 and P =.011). Plasma BA and FGF19 levels significantly increased after CDCA administration (P = .001 and P < .001).
  
  
  CONCLUSIONS
  CDCA modulates GLP-1 and CCK secretion; the effect is small and does not influence glucose levels. The marked increase in plasma BAs and the attenuated insulin release after the oGTT indicate the role of BAs in glycemic control, independent of the incretin axis, and suggest involvement of farnesoid X receptor activation pathways.
authors.affiliation: Department of Biomedicine, University Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: A C
authors.initials: AC
authors.lastname: Meyer-Gerspach
authors.forename: R E
authors.initials: RE
authors.lastname: Steinert
authors.forename: S
authors.initials: S
authors.lastname: Keller
authors.forename: A
authors.initials: A
authors.lastname: Malarski
authors.forename: F H
authors.initials: FH
authors.lastname: Schulte
authors.forename: C
authors.initials: C
authors.lastname: Beglinger
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood; D002096:C-Peptide / Q000032:analysis; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D002766:Cholecystokinin / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism*; D004311:Double-Blind Method; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D002096:C-Peptide; D004151:Dipeptides; D007328:Insulin; D002635:Chenodeoxycholic Acid; C042696:tyrosyltyrosine; D005346:Fibroblast Growth Factors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin