The Dietary Furocoumarin Imperatorin Increases Plasma GLP-1 Levels in Type 1-Like Diabetic Rats.
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.
['Wang|Lin-Yu|LY|', 'Cheng|Kai-Chun|KC|', 'Li|Yingxiao|Y|', 'Niu|Chiang-Shan|CS|', 'Cheng|Juei-Tang|JT|', 'Niu|Ho-Shan|HS|']
D000818:Animals D001786:Blood Glucose D016466:CHO Cells D002460:Cell Line D003412:Cricetulus D003921:Diabetes Mellitus, Experimental D004305:Dose-Response Relationship, Drug D011564:Furocoumarins D020868:Gene Silencing D052216:Glucagon-Like Peptide 1 D006801:Humans D007328:Insulin D008297:Male D051381:Rats D017207:Rats, Sprague-Dawley D043562:Receptors, G-Protein-Coupled
imperatorin GPR119 TGR5 transfection triamterene sitagliptin