Department of Childhood Education and Nursery, Chia Nan University of Pharmacy and Science, Rende, Tainan City 71710, Taiwan.
Division of Pediatrics, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan.
Nutrients. 2017 Oct 30;9(11):1192. doi: 10.3390/nu9111192.
Imperatorin, a dietary furocoumarin, is found not only in medicinal plants, but also in popular culinary herbs, such as parsley and fennel. Recently, imperatorin has been shown to activate GPR119 in cells. Another GPR, GPR131, also called TGR5 or G-protein-coupled bile acid receptor 1 (GPBAR1), is known to regulate glucose metabolism. Additionally, TGR5 activation increases glucagon-like peptide (GLP-1) secretion to lower blood sugar levels in animals. Therefore, the present study aims to determine whether the effects of imperatorin on GLP-1 secretion are mediated by TGR5. First, we transfected cultured Chinese hamster ovary cells (CHO-K1 cells) with the TGR5 gene. Glucose uptake was confirmed in the transfected cells using a fluorescent indicator. Moreover, NCI-H716 cells, which secrete GLP-1, were used to investigate the changes in calcium concentrations and GLP-1 levels. In addition, streptozotocin (STZ)-induced type 1-like diabetic rats were used to identify the effects of imperatorin in vivo. Imperatorin dose-dependently increased glucose uptake in CHO-K1 cells expressing TGR5. In STZ diabetic rats, similar to the results in NCI-H716 cells, imperatorin induced a marked increase of GLP-1 secretion that was reduced, but not totally abolished, by a dose of triamterene that inhibited TGR5. Moreover, increases in GLP-1 secretion induced by imperatorin and GPR119 activation were shown in NCI-H716 cells. We demonstrated that imperatorin induced GLP-1 secretion via activating TGR5 and GPR119. Therefore, imperatorin shall be considered as a TGR5 and GPR119 agonist.
欧前胡素，一种饮食中的呋喃香豆素，不仅存在于药用植物中，也存在于流行的烹饪香草中，如香菜和茴香。最近，研究表明欧前胡素可以在细胞中激活 GPR119。另一种 GPR，GPR131，也称为 TGR5 或 G 蛋白偶联胆汁酸受体 1（GPBAR1），已知可调节葡萄糖代谢。此外，TGR5 激活可增加胰高血糖素样肽（GLP-1）的分泌，从而降低动物的血糖水平。因此，本研究旨在确定欧前胡素对 GLP-1 分泌的作用是否通过 TGR5 介导。首先，我们将 TGR5 基因转染到培养的中国仓鼠卵巢细胞（CHO-K1 细胞）中。通过荧光指示剂确认转染细胞中的葡萄糖摄取。此外，使用分泌 GLP-1 的 NCI-H716 细胞来研究钙浓度和 GLP-1 水平的变化。另外，使用链脲佐菌素（STZ）诱导的 1 型糖尿病样大鼠来鉴定欧前胡素在体内的作用。欧前胡素呈剂量依赖性增加表达 TGR5 的 CHO-K1 细胞中的葡萄糖摄取。在 STZ 糖尿病大鼠中，与 NCI-H716 细胞的结果相似，欧前胡素诱导 GLP-1 分泌显著增加，而用抑制 TGR5 的三氨喋呤抑制，但未完全消除。此外，在 NCI-H716 细胞中显示了欧前胡素和 GPR119 激活诱导的 GLP-1 分泌增加。我们证明欧前胡素通过激活 TGR5 和 GPR119 诱导 GLP-1 分泌。因此，欧前胡素应被视为 TGR5 和 GPR119 的激动剂。
