Identification of berberine as a novel agonist of fatty acid receptor GPR40.
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.
Rayasam
Geetha Vani
GV
Department of Pharmacology, Novel Drug Discovery Research, R&D III RANBAXY, Plot 20, Sector 18, Gurgaon, Haryana, India. gvrayasam@yahoo.com
Tulasi
Vamshi Krishna
VK
Sundaram
Sindhuja
S
Singh
Winny
W
Kant
Rajiv
R
Davis
Joseph Alex
JA
Saini
Kulvinder Singh
KS
Ray
Abhijit
A
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*
C473035:G-protein-coupled receptor 40, rat; D007004:Hypoglycemic Agents; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D001599:Berberine; D005947:Glucose; D002118:Calcium