8 research outputs found
Chenodeoxycholic acid stimulates glucagon-like peptide-1 secretion in patients after Roux-en-Y gastric bypass
Postprandial secretion of glucagonâlike peptideâ1 (GLPâ1) is enhanced after RouxâenâY gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLPâ1 secretion through activation of TGR5âreceptors. We aimed to evaluate GLPâ1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGBâoperated participants. Eleven participants (BMI 29.1 ¹ 1.2, age 37.0 ¹ 3.2 years, time from RYGB 32.3 ¹ 1.1 months, weight loss after RYGB 37.0 ¹ 3.1 kg) were studied in a placeboâcontrolled, crossoverâstudy. On three different days, participants ingested (1) placebo (water), (2) UDCA 750 mg, (3) CDCA 1250 mg (highest recommended doses). Oral intake of CDCA increased plasma concentrations of GLPâ1, Câpeptide, glucagon, peptide YY, neurotensin, total bile acids, and fibroblast growth factor 19 significantly compared with placebo (all P < 0.05 for peak and positive incremental areaâunderâtheâcurve (piAUC)). All plasma hormone concentrations were unaffected by UDCA. Neither UDCA nor CDCA changed glucose, cholecystokinin or glucoseâdependent insulinotropic polypeptide (GIP) concentrations. In conclusion, our findings demonstrate that the primary bile acid chenodeoxycholic acid is able to enhance secretion of gut hormones when administered orally in RYGBâoperated patientsâeven in the absence of nutrients
Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass
Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery
Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery
Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass
BACKGROUND: Altered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly via stimulation of GLP-1 secretion. We investigated the role of exogenous as well as endogenous BAs for GLP-1 secretion after RYGB by administering chenodeoxycholic acid (CDCA) and the BA sequestrant colesevelam (COL) both in the presence and the absence of a meal stimulus. METHODS: Two single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200Â ml water with 1) CDCA 1.25Â g or 2) CDCA 1.25Â g + colesevelam 3.75Â g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25Â g, 2) COL 3.75Â g or 3) COL 3.75Â g Ă 2, or 4) no additions. RESULTS: In study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones. CONCLUSION: In RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB