This was evidenced by GPRC6A β-cell-cko mice, which exhibited lower circulating insulin levels and impaired glucose tolerance.29 Further studies have shown that unOCN activates ERK and cAMP second messenger pathways in GPRC6A-expressing cells in a dose-dependent manner but not in GPRC6A knockout cells.49 These results suggest that unOCN regulates energy metabolism by binding to the GPRC6A receptor and activating a series of downstream signal transduction pathways, such as ERK, cAMP, PI3K/Akt/mTOR, and AMPK.48,50–53. The gene discussed is GPRC6A; the disease is Impaired glucose tolerance.