Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Front Endocrinol (Lausanne). 2021 May 14;12:681116. doi: 10.3389/fendo.2021.681116. eCollection 2021.
Altered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly 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.
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.
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.
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.
胆汁酸（BA）代谢的改变被认为参与了 Roux-en-Y 胃旁路术（RYGB）后葡萄糖调节的改善，可能是通过刺激 GLP-1 的分泌。我们通过给予鹅脱氧胆酸（CDCA）和 BA 螯合剂考来烯胺（COL），并在存在和不存在餐食刺激的情况下，研究了外源性和内源性 BAs 对 RYGB 后 GLP-1 分泌的作用。
进行了两项单盲随机交叉研究。在研究 1 中，8 名 RYGB 手术患者分别在 2 天内饮用 200ml 水，其中 1）CDCA 1.25g 或 2）CDCA 1.25g+考来烯胺 3.75g。在研究 2 中，12 名 RYGB 参与者分别在 2 天内饮用添加 1）CDCA 1.25g、2）COL 3.75g 或 3）COL 3.75g×2 或 4）无添加物的混合餐。
在研究 1 中，口服 CDCA 增加了循环 BAs、GLP-1、C 肽、胰高血糖素和神经降压素。考来烯胺的添加降低了所有反应。在研究 2 中，添加 CDCA 增强了餐食诱导的血浆 GLP-1、胰高血糖素和 FGF-19 的增加，并降低了血浆葡萄糖和 C 肽浓度，而添加考来烯胺降低了循环 BAs，但对餐食诱导的血浆葡萄糖或测量的胃肠激素变化没有影响。
在 RYGB 手术后患者中，外源性 CDCA 增强了餐食刺激的 GLP-1 和胰高血糖素分泌，但不影响胰岛素分泌，而 BA 螯合剂考来烯胺降低了 CDCA 刺激的 GLP-1 分泌，但不影响餐食刺激的 GLP-1、C 肽或胰高血糖素分泌或葡萄糖耐量。这些发现表明内源性胆汁酸在 RYGB 后餐后肠道激素分泌或葡萄糖代谢的急性调节中作用有限。
