期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 62, 期 8, 页码 -出版社
WILEY
DOI: 10.1002/mnfr.201700770
关键词
computational modeling; EGCG; gallic acid; GPCR; GPRC6A
资金
- National Institutes of Health [R01-AR37308]
- Americans Diabetes Association [1-13-BS-149-BR]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR037308] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK095812] Funding Source: NIH RePORTER
Scope: The molecular mechanisms whereby gallates in green tea exert metabolic effects are poorly understood. Methods and results: We found that GPRC6A, a multi-ligand-sensing G-protein-coupled receptor that regulates energy metabolism, sex hormone production, and prostate cancer progression, is a target for gallates. Sodium gallate (SG), gallic acid (GA) > ethyl gallate (EG) > octyl gallate (OG) dose dependently activated ERK in HEK-293 cells transfected with GPRC6A but not in non-transfected controls. SG also stimulated insulin secretion in beta-cells isolated from wild-type mice similar to the endogenous GPRC6A ligands, osteocalcin (Ocn) and testosterone (T). Side-chain additions to create OG resulted in loss of GPRC6A agonist activity. Another component of green tea, epigallocatechin 3-gallate (EGCG), dose-dependently inhibited Ocn activation of GPRC6A in HEK-293 cells transfected with GPRC6A and blocked the effect of Ocn in stimulating glucose production in CH10T1/2 cells. Using structural models of the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A, calculations suggest that l-amino acids and GA bind to the VFT, whereas EGCG is calculated to bind to sites in both the VFT and 7-TM. Conclusion: GA and EGCG have offsetting agonist and antagonist effects on GPRC6A that may account for the variable metabolic effect of green tea consumption.
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