title: Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways.
abstract: Our previous studies revealed that berberine-mediated GLP-1 secretion was a possible mechanism for berberine exerting good effects on hyperglycemia. This study was designed to ascertain whether berberine-induced secretion of GLP-1 was related with activation of bitter taste receptors expressed in gastrointestinal tract. Western blotting results showed that TAS2R38, a subtype of bitter taste receptor, was expressed on human enteroendocrine NCI-H716 cells. GLP-1 secretion induced by berberine from NCI-H716 cells was inhibited by incubation with anti-TAS2R38 antibody. We further performed gene silencing using siRNA to knockdown TAS2R38 from NCI-H716 cells, which showed that siRNA knockdown of the TAS2R38 reduced berberine-mediated GLP-1 secretion. We adopted inhibitors of PLC and TRPM5 known to be involved in bitter taste transduction to investigate the underlying pathways mediated in berberine-induced GLP-1 secretion. It was found that PLC inhibitor U73122 inhibited berberine-induced GLP-1 release in NCI-H716 cells, while TRPM5 blocker quinine failed to attenuate berberine-induced secretion of GLP-1. The present results demonstrated that berberine stimulated GLP-1 secretion via activation of gut-expressed bitter taste receptors in a PLC-dependent manner. Because berberine was found to be a ligand of bitter taste receptor, the results of present study may provide an explanation for some bitter taste substance obtain hypoglycemic effect.
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: haoyyl0902@163.com.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Suzhou Institute for Food and Drug Control, 215104, PR China. Electronic address: haogang531@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Hao
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: zhangquanying@163.com.
authors.forename: Quanying
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: huawenyan2010@163.com.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: enigmatz@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: zwjaja@163.com.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: zslynsz@126.com.
authors.forename: Shunlin
authors.initials: S
authors.lastname: Zong
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China. Electronic address: dreamboyhmhm@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.affiliation: Jiangsu Province Hospital of Traditional Chinese Medicine, 210029, PR China. Electronic address: 183553076@qq.com.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Wen
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013649:Taste / Q000187:drug effects* / Q000502:physiology; D013650:Taste Buds / Q000187:drug effects / Q000378:metabolism; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D001599:Berberine; D052216:Glucagon-Like Peptide 1
keywords: Berberine; Bitter taste receptor; Diabetes; Glucagon-like peptide 1; PLC pathway