ArticlePloS one2008
GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.
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Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.
- Pooled it
- The relationship between circulating osteocalcin and muscle mass measurements in humans: A systematic review and meta-analysis.Sports medicine and health science · 2026Review
- Article
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 2025Review
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.Development (Cambridge, England) · 2024Article
- Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling.FASEB bioAdvances · 2024Article
- GPRC6A is a Potential Therapeutic Target for Metformin Regulation of Glucose Homeostasis in Mice.bioRxiv : the preprint server for biology · 2024Article
- Osteocalcin: Beyond Bones.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.Nature metabolism · 2024Article
- A trend of osteocalcin in diabetes mellitus research: bibliometric and visualization analysis.Frontiers in endocrinology · 2024Article
- Messages from the Mineral: How Bone Cells Communicate with Other Tissues.Calcified tissue international · 2023Review
- Anti-inflammatory role of extracellular l-arginine through calcium sensing receptor in human renal proximal tubular epithelial (HK-2) cells.International immunopharmacology · 2023Article
- Article
- RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function.Journal of endocrinological investigation · 2022Article
- Untargeted Metabolomics Reveals the Function of GPRC6A in Amino Acid and Lipid Metabolism in Mice.Metabolites · 2022Article
- GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice.Metabolites · 2022Article
- Undercarboxylated, But Not Carboxylated, Osteocalcin Suppresses TNF-α-Induced Inflammatory Signaling Pathway in Myoblasts.Journal of the Endocrine Society · 2022Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown. METHODS/PRINCIPAL
findingsIn this study, we created and characterized the phenotype of GPRC6A(-/-) mice. We observed complex metabolic abnormalities in GPRC6A(-/-) mice involving multiple organ systems that express GPRC6A, including bone, kidney, testes, and liver. GPRC6A(-/-) mice exhibited hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance. In addition, we observed high expression of GPRC6A in Leydig cells in the testis. Ablation of GPRC6A resulted in feminization of male GPRC6A(-/-) mice in association with decreased lean body mass, increased fat mass, increased circulating levels of estradiol, and reduced levels of testosterone. GPRC6A was also highly expressed in kidney proximal and distal tubules, and GPRC6A(-/-) mice exhibited increments in urine Ca/Cr and PO(4)/Cr ratios as well as low molecular weight proteinuria. Finally, GPRC6A(-/-) mice exhibited a decrease in bone mineral density (BMD) in association with impaired mineralization of bone. CONCLUSIONS/SIGNIFICANCE: GPRC6A(-/-) mice have a metabolic syndrome characterized by defective osteoblast-mediated bone mineralization, abnormal renal handling of calcium and phosphorus, fatty liver, glucose intolerance and disordered steroidogenesis. These findings suggest the overall function of GPRC6A may be to coordinate the anabolic responses of multiple tissues through the sensing of extracellular amino acids, osteocalcin and divalent cations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.