Division of Cardiology, Department of Internal Medicine, Chung Hsing Branch of Taipei City Hospital, Taipei City, Taiwan, 10341.
Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, Taiwan, 97005.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Nov;390(11):1097-1104. doi: 10.1007/s00210-017-1409-9. Epub 2017 Jul 30.
Endogenous Takeda G-protein-coupled receptor 5 (TGR5), G-protein-coupled bile acid receptor 1 (GPBAR1), regulates glucose metabolism. In animals, TGR5 activation by a chemical agonist may increase incretin secretion and reduce the blood sugar level. Recently, betulinic acid has been suggested to activate TGR5. Ursolic acid is a well-known pentacyclic triterpenoid that is similar to betulinic acid. It is of special interest to determine the potential effect of ursolic acid on TGR5. Therefore, we transfected cultured Chinese hamster ovary (CHO-K1) cells with the TGR5 gene. The functions of the transfected cells were confirmed via glucose uptake using a fluorescent indicator. Moreover, NCI-H716 cells that secreted incretin were also investigated, and the glucagon-like peptide (GLP-1) levels were quantified using ELISA kits. In addition, streptozotocin (STZ)-induced type 1-like diabetic rats were used to identify the effect of ursolic acid in vivo. Ursolic acid concentration dependently increased glucose uptake in CHO-K1 cells expressing TGR5. In NCI-H716 cells, ursolic acid induced a concentration-dependent elevation in GLP-1 secretion, which was inhibited by triamterene at the effective concentrations to block TGR5. Ursolic acid also increased the plasma GLP-1 level via TGR5 activation, which was further characterized in vivo with type 1-like diabetic rats. Moreover, ursolic acid is more effective than betulinic acid in reduction of hyperglycemia and increase of GLP-1 secretion. Therefore, we demonstrated that ursolic acid can activate TGR5, enhancing GLP-1 secretion in vitro and in vivo. Therefore, ursolic acid is suitable for use in TGR5 activation.
内源性 Takeda G 蛋白偶联受体 5（TGR5）、G 蛋白偶联胆汁酸受体 1（GPBAR1）调节葡萄糖代谢。在动物中，化学激动剂激活 TGR5 可能会增加肠促胰岛素分泌并降低血糖水平。最近，桦木酸被认为可以激活 TGR5。熊果酸是一种众所周知的五环三萜，与桦木酸相似。确定熊果酸对 TGR5 的潜在影响特别有趣。因此，我们将 TGR5 基因转染到培养的中国仓鼠卵巢（CHO-K1）细胞中。通过使用荧光指示剂检测葡萄糖摄取来确认转染细胞的功能。此外，还研究了分泌肠促胰岛素的 NCI-H716 细胞，并使用 ELISA 试剂盒定量测定胰高血糖素样肽（GLP-1）水平。此外，还使用链脲佐菌素（STZ）诱导的 1 型糖尿病样大鼠来鉴定熊果酸在体内的作用。熊果酸浓度依赖性地增加表达 TGR5 的 CHO-K1 细胞中的葡萄糖摄取。在 NCI-H716 细胞中，熊果酸诱导 GLP-1 分泌浓度依赖性升高，三氨喋呤在有效浓度下抑制 TGR5 可抑制其升高。熊果酸还通过激活 TGR5 增加血浆 GLP-1 水平，这在 1 型糖尿病样大鼠体内得到进一步表征。此外，熊果酸在降低高血糖和增加 GLP-1 分泌方面比桦木酸更有效。因此，我们证明了熊果酸可以激活 TGR5，体外和体内均可增强 GLP-1 分泌。因此，熊果酸适合用于 TGR5 激活。
