ArticleEndocrinology2016
Evidence for Osteocalcin Binding and Activation of GPRC6A in β-Cells.
Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: a systematic review and meta-analysis of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Comprehensive metabolic characterization of serum osteocalcin action in a large non-diabetic sample.PloS one · 2017Trial
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Halved but Potent: Exploring the Inhibitory Property of Curcumin Derivatives Against Evolving SARS-CoV-2 Strains.The protein journal · 2026Article
- Osteocalcin Beyond Bone: Molecular Mechanisms, Endocrine Networks, and Translational Perspectives Across Metabolism, Neurobiology, and Chronic Disease.International journal of molecular sciences · 2026Review
- Update and Reassessment of Data on the Role of Osteocalcin in Bone Properties and Glucose Homeostasis in OC-/- Mice.International journal of molecular sciences · 2025Review
- ucOCN Promotes Testosterone Synthesis via the PKA-MAPK/ERK-CREB Signaling Pathway in Porcine Leydig Cells.Cells · 2025Article
- Differential Features of Cholecystokinin-Releasing Peptides Derived from Food Proteins: Peptide Length, Amino Acid Composition and Primary Structure; Analysis of Currently Identified Peptide Sequences.International journal of molecular sciences · 2025Article
- Two decades into the crosstalk between bone and energy metabolism.Nature reviews. Endocrinology · 2025Article
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Osteocalcin induces phosphorylation of FOXO1 in human beta-cells and restores insulin expression under hyperglycemic conditions.Research square · 2025Article
- Pharmacological and resting state fMRI reveal Osteocalcin's effects on mouse brain regions with high Gpr37 and Gpr158 expression.Scientific reports · 2025Article
- Association between osteocalcin and residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes: a pivotal study.Journal of endocrinological investigation · 2025Article
- Metabolic shifts in ratio of ucOcn to cOcn toward bone resorption contribute to age-dependent bone loss in male mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- Total osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic-pituitary-gonadal axis activation in Klinefelter syndrome.Journal of endocrinological investigation · 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
- Hyperglycemia from Diabetes Potentiates Uncarboxylated Osteocalcin-Stimulated Insulin Secretion in Rat INS-1 Pancreatic β-Cells.Nutrients · 2024Article
- Extrahepatic Vitamin K-Dependent Gla-Proteins-Potential Cardiometabolic Biomarkers.International journal of molecular sciences · 2024Review
- Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.EMBO reports · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The possibility that G protein-coupled receptor family C member A (GPRC6A) is the osteocalcin (Ocn)-sensing G protein-coupled receptor that directly regulates pancreatic β-cell functions is controversial. In the current study, we found that Ocn and an Ocn-derived C-terminal hexapeptide directly activate GPRC6A-dependent ERK signaling in vitro. Computational models probe the structural basis of Ocn binding to GPRC6A and predict that the C-terminal hexapeptide docks to the extracellular side of the transmembrane domain of GPRC6A. Consistent with the modeling, mutations in the computationally identified binding pocket of GPRC6A reduced Ocn and C-terminal hexapeptide activation of this receptor. In addition, selective deletion of Gprc6a in β-cells (Gprc6a(β)(-cell-cko)) by crossing Gprc6a(flox/flox) mice with Ins2-Cre mice resulted in reduced pancreatic weight, islet number, insulin protein content, and insulin message expression. Both islet size and β-cell proliferation were reduced in Gprc6a(β)(-cell-cko) compared with control mice. Gprc6a(β)(-cell-cko) exhibited abnormal glucose tolerance, but normal insulin sensitivity. Islets isolated from Gprc6a(β)(-cell-cko) mice showed reduced insulin simulation index in response to Ocn. These data establish the structural basis for Ocn direct activation of GPRC6A and confirm a role for GPRC6A in regulating β-cell proliferation and insulin secretion.
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What OpenQuestion holds
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.