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A, Ocn released from bone resorption activates GPRC6A to regulate insulin secretion in β-cells. Insulin stimulates bone resorption releasing bioactive Ocn. GPRC6A may also be a receptor shared by nutrients (B) and testosterone, which stimulates insulin secretion (C). In addition, Ocn may target GPRC6A in other tissues to regulate testosterone production (C) and to promote insulin sensitivity (D). GPRC6A ligands may also regulate LH production.
