Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion
Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion
复制标题
DOI：
10.1111/dom.12648
复制
发表时间：
2016-06-01
影响因子：
5.8
通讯作者：
Knop, F. K.
中科院分区：
文献类型：
--
作者：
Hansen, M.;Scheltema, M. J.;Knop, F. K.
目的：探讨人胆汁酸主成分鹅去氧胆酸(CDCA)和胆汁酸阻滞剂(BAS)考昔韦仑灌胃对血浆胰高血糖素样肽-1(GLP-1)、葡萄糖、胰岛素、C-肽、胰高血糖素、胆囊素和胃泌素水平的影响，以及对胃排空、胆囊量、食欲和食物摄入量的影响。方法：9例2型糖尿病患者和10名健康对照组分别灌胃给予CDCA、(II)Colevelam和(II)Colevelam。(Iii)CDCA+Colesevelam或(Iv)安慰剂。结果：在2型糖尿病组和健康对照组中，CDCA组的GLP-1水平分别高于科莱维仑组、CDCA+科莱维仑组和安慰剂组(p<；0.05)。这些干预措施没有影响任何一组的血糖、胰岛素或C-肽浓度。在两组中，CDCA引起的血浆胰岛素/血糖比均较可来维仑、CDCA+可来维仑和安慰剂略有升高。结论：CDCA可增加GLP-1和GLP-1的分泌，延迟胃排空。我们推测，胆汁酸诱导的L细胞TGR5的激活增加了GLP-1的分泌，进而可能导致葡萄糖刺激的胰岛素分泌的放大。此外，我们的数据表明，可来福仑对人类GLP-1的分泌没有明显影响。
Aim: To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide, glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake.Methods: On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled.Results: In both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP-1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C-peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups.Conclusions: CDCA increased GLP-1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid-induced activation of TGR5 on L cells increases GLP-1 secretion, which, in turn, may result in amplification of glucose-stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP-1 secretion in humans.