School of Biological Sciences, Queen's University Belfast, BT9 5AG, UK.
Biol Chem. 2011 Apr;392(6):539-46. doi: 10.1515/BC.2011.050. Epub 2011 Apr 27.
Physiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1 in vitro in STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected for in vivo studies in normal and GLP-1R(-/-) mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal mice and by 27% in GLP-1R(-/-) mice, and plasma GLP-1 concentrations were significantly elevated 30 min post-gavage. Additional studies used incretin receptor antagonists to probe involvement of GLP-1 and GIP in taurocholic acid-induced glucose lowering. The findings suggest that bile acids partially aid glucose regulation by physiologically enhancing nutrient-induced GLP-1 secretion. However, GLP-1 secretion appears to be only part of the glucose-lowering mechanism and our studies indicate that the other major incretin GIP is not involved.
胆汁酸的生理分泌先前与血糖调节有关。GLP-1 是一种具有重要降血糖作用的肠肽激素，例如刺激胰岛素分泌和抑制胰高血糖素分泌。在这项研究中，我们评估了几种胆汁酸化合物在 STC-1 细胞中体外分泌 GLP-1 的能力。胆汁酸刺激 GLP-1 分泌增加了 3.3 至 6.2 倍，但有些与细胞毒性作用有关。甘胆酸和牛磺胆酸被选为正常和 GLP-1R(-/-)小鼠体内研究的候选药物。口服葡萄糖耐量试验显示，甘胆酸对葡萄糖波动没有影响。然而，牛磺胆酸可使正常小鼠的葡萄糖波动降低 40%，GLP-1R(-/-)小鼠的葡萄糖波动降低 27%，并且在灌胃后 30 分钟时血浆 GLP-1 浓度显著升高。其他研究使用肠促胰岛素受体拮抗剂来探讨 GLP-1 和 GIP 在牛磺胆酸诱导的血糖降低中的作用。研究结果表明，胆汁酸通过生理上增强营养诱导的 GLP-1 分泌，部分有助于葡萄糖调节。然而，GLP-1 分泌似乎只是降低血糖机制的一部分，我们的研究表明另一种主要的肠促胰岛素 GIP 不参与其中。
