Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass
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Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass. / Jonsson, Isabella; Bojsen-Moller, Kirstine N.; Kristiansen, Viggo B.; Veedfald, Simon; Albrechtsen, Nicolai J. Wewer; Clausen, Trine R.; Kuhre, Rune E.; Rehfeld, Jens F.; Holst, Jens J.; Madsbad, Sten; Svane, Maria S.
I: Frontiers in Endocrinology, Bind 12, 681116, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass
AU - Jonsson, Isabella
AU - Bojsen-Moller, Kirstine N.
AU - Kristiansen, Viggo B.
AU - Veedfald, Simon
AU - Albrechtsen, Nicolai J. Wewer
AU - Clausen, Trine R.
AU - Kuhre, Rune E.
AU - Rehfeld, Jens F.
AU - Holst, Jens J.
AU - Madsbad, Sten
AU - Svane, Maria S.
PY - 2021
Y1 - 2021
N2 - BackgroundAltered 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.MethodsTwo 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 x 2, or 4) no additions.ResultsIn 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.ConclusionIn 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.
AB - BackgroundAltered 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.MethodsTwo 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 x 2, or 4) no additions.ResultsIn 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.ConclusionIn 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.
KW - bile acids
KW - colesevelam
KW - RYGB
KW - Roux-en-Y gastric bypass
KW - glucagon-like peptide 1
U2 - 10.3389/fendo.2021.681116
DO - 10.3389/fendo.2021.681116
M3 - Journal article
C2 - 34084153
VL - 12
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 681116
ER -
ID: 271688265