Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass

Abstract

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 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 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.

Keywords: RYGB; Roux-en-Y gastric bypass; bile acids; colesevelam; glucagon-like peptide 1.

Conflict of interest statement

RK works for Novo Nordisk A/S, but was at the time of his contribution exclusively employed by University of Copenhagen. TC works for Novo Nordisk A/S and own shares in Novo Nordisk A/S and Zealand Pharma A/S. All other authors declare no conflict of interest in relation to the current manuscript.

Copyright © 2021 Jonsson, Bojsen-Møller, Kristiansen, Veedfald, Wewer Albrechtsen, Clausen, Kuhre, Rehfeld, Holst, Madsbad and Svane.

Figures

Figure 1

Concentrations of (A) total bile acids, (B) plasma glucose, (C) GLP-1, (D) C-peptide, (E) glucagon, (F) neurotensin, (G) cholecystokinin, and (H) FGF-19 following ingestion of chenodeoxycholic acid (CDCA) or CDCA in combination with the bile acid sequestrant colesevelam (COL) suspended in water (CDCA + COL), n = 8. Data are mean ± SEM.

Figure 2

Plasma concentrations of (A) total bile acids and (B) total bile acids (without the CDCA concentration curve drawn) following ingestion of a mixed meal alone (Meal), mixed meal in combination with CDCA added to the meal (Meal + CDCA), mixed meal in combination with COL added to the meal (Meal + COL), or mixed meal in combination with COL administered both the night before the study day as tablets and added to the meal (Meal + COL × 2), n = 12. Data are mean ± SEM.

Figure 3

Concentrations of (A) plasma glucose, (B) serum C-peptide, (C) glucagon, (D) GLP-1, (E) neurotensin, (F) FGF-19, (G) CCK and (H) paracetamol following ingestion of a mixed meal alone (Meal), mixed meal in combination with CDCA with the meal (Meal + CDCA), mixed meal in combination with COL added to the meal (Meal + COL), or mixed meal in combination with COL administered both the night before the study day as tablets and added to the meal (Meal + COL × 2), n = 12. Data are mean ± SEM.