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Effects of chenodeoxycholic acid on the secretion of gut peptides and fibroblast growth factors in healthy humans

Meyer-Gerspach, A. C. and Steinert, R. E. and Keller, S. and Malarski, A. and Schulte, F. H. and Beglinger, C.. (2013) Effects of chenodeoxycholic acid on the secretion of gut peptides and fibroblast growth factors in healthy humans. Journal of clinical endocrinology and metabolism, Vol. 98, H. 8. pp. 3351-3358.

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Official URL: http://edoc.unibas.ch/dok/A6338736

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Abstract

CONTEXT: 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. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: 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. MAIN OUTCOME MEASURES: 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Gastroenterology (Beglinger)
UniBasel Contributors:Beglinger, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Thomas
ISSN:0021-972X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:10 Apr 2015 09:13

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