Natural compounds gallic acid, sodium gallate, and EGCG are agonists or antagonists of GPRC6A. A) Chemical structures of gallates and EGCG. B) Gallic acid and C) ethyl gallate stimulated GPRC6A mediated ERK phosphorylation, but not C) octyl gallate and D) EGCG in HEK-293 stably transfected with GPRC6A cDNA, but the stimulation of SG, GA, and EG were not appealed in control HEK-293 without GPRC6A cDNA. The bar graph in the bottom panels depicts the fold-increase in ERK activation in response to Ocn, T, GA, EG, OG, and EGCG in control HEK-293 and HEK-293 transfected with GPRC6A cDNA. E) SG (1 μm) stimulated insulin secretion in mouse isolated islets. Values represent the mean ± SEM. * indicates significant differences from control and stimulated groups at p < 0.05 (n ≥ 4).