title: Identification of berberine as a novel agonist of fatty acid receptor GPR40.
abstract: Several herbal plants such as Chinese herb Rhizoma Coptidis have been reported to possess antidiabetic activity. Berberine is its major active constituent and functions as an insulin sensitizer and insulin secretagogue. It has been reported to modulate several signaling pathways and targets. The objective of the current study is to investigate if berberine can function as a ligand of fatty acid receptor GPR40, which stimulates glucose dependent insulin secretion. Towards this objective, a mammalian cell line with stable overexpression of GPR40 was generated and characterized. Berberine stimulated calcium mobilization with an EC(50) of 0.76 microM in this GPR40 overexpressing cell line. Further, berberine stimulated glucose dependent insulin secretion from rat pancreatic beta cell line. This suggests that berberine functions as an agonist of fatty acid receptor GPR40 and might be a novel antidiabetic mechanism of action for berberine.
authors.affiliation: Department of Pharmacology, Novel Drug Discovery Research, R&D III RANBAXY, Plot 20, Sector 18, Gurgaon, Haryana, India. gvrayasam@yahoo.com
authors.forename: Geetha Vani
authors.initials: GV
authors.lastname: Rayasam
authors.forename: Vamshi Krishna
authors.initials: VK
authors.lastname: Tulasi
authors.forename: Sindhuja
authors.initials: S
authors.lastname: Sundaram
authors.forename: Winny
authors.initials: W
authors.lastname: Singh
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kant
authors.forename: Joseph Alex
authors.initials: JA
authors.lastname: Davis
authors.forename: Kulvinder Singh
authors.initials: KS
authors.lastname: Saini
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*
chemical_list: C473035:G-protein-coupled receptor 40, rat; D007004:Hypoglycemic Agents; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D001599:Berberine; D005947:Glucose; D002118:Calcium