Abstract
Postprandial secretion of glucagon‐like peptide‐1 (GLP‐1) is enhanced after Roux‐en‐Y 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 GLP‐1 secretion through activation of TGR5‐receptors. We aimed to evaluate GLP‐1 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 RYGB‐operated participants. Eleven participants (BMI 29.1 ± 1.2, age 37.0 ± 3.2 years, time from RYGB 32.3 ± 1.1 months, weight loss after RYGB 37.0 ± 3.1 kg) were studied in a placebo‐controlled, crossover‐study. 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 GLP‐1, C‐peptide, 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 area‐under‐the‐curve (piAUC)). All plasma hormone concentrations were unaffected by UDCA. Neither UDCA nor CDCA changed glucose, cholecystokinin or glucose‐dependent 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 RYGB‐operated patients—even in the absence of nutrients.
Highlights
Roux-en-Y gastric bypass (RYGB) is an effective treatment of severe obesity (Sjo€stro€m 2013; Madsbad et al 2014) and type 2 diabetes (Madsbad et al 2014; Schauer et al 2014)
We aimed to evaluate glucagon-like peptide-1 (GLP-1) secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) in RYGB-operated participants
We investigated the effects of oral administration of two different bile acids (BAs), ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in RYGB-operated participants
Summary
Roux-en-Y gastric bypass (RYGB) is an effective treatment of severe obesity (Sjo€stro€m 2013; Madsbad et al 2014) and type 2 diabetes (Madsbad et al 2014; Schauer et al 2014). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. Bile Acids Stimulate GLP-1 Secretion after RYGB insulin secretion (Jacobsen et al 2012) all appear to contribute to the weight loss and improved glucose metabolism seen postoperatively. After RYGB, studies have consistently reported a 7–10 fold enhanced postprandial secretion of glucagon-like peptide-1 (GLP-1), which is of major importance for the improved beta-cell function in patients with preoperative type 2 diabetes (Jørgensen et al 2012, 2013) and linked to postoperative weight loss (Dirksen et al 2012). The mechanisms behind the enhanced GLP-1 secretion after RYGB remain poorly understood
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