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The Role of Osteocalcin in Human Glucose Metabolism: Marker or Mediator?

Overview
Specialty Endocrinology
Date 2012 Nov 14
PMID 23147574
Citations 105
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Abstract

Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent, γ-carboxylated form. The concentration of osteocalcin in the circulation is a measure of bone formation. The undercarboxylated form of osteocalcin is active in glucose metabolism in mice. Total serum osteocalcin concentrations in humans are inversely associated with measures of glucose metabolism; however, human data are inconclusive with regard to the role of uncarboxylated osteocalcin in glucose metabolism because most studies do not account for the influence of vitamin K on the proportion of undercarboxylated osteocalcin or differentiate between the total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do not concomitantly measure other bone turnover markers to isolate the role of osteocalcin as a measure of bone formation from its effect on glucose metabolism. Carefully designed studies are required to define the role of osteocalcin and its carboxylated or undercarboxylated forms in the regulation of glucose metabolism in humans.

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References
1.
Takada I, Mihara M, Suzawa M, Ohtake F, Kobayashi S, Igarashi M . A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation. Nat Cell Biol. 2007; 9(11):1273-85. DOI: 10.1038/ncb1647. View

2.
Wellendorph P, Brauner-Osborne H . Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene. 2004; 335:37-46. DOI: 10.1016/j.gene.2004.03.003. View

3.
Stenflo J, Fernlund P, Egan W, Roepstorff P . Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci U S A. 1974; 71(7):2730-3. PMC: 388542. DOI: 10.1073/pnas.71.7.2730. View

4.
Desbois C, Hogue D, Karsenty G . The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression. J Biol Chem. 1994; 269(2):1183-90. View

5.
Mega J . A new era for anticoagulation in atrial fibrillation. N Engl J Med. 2011; 365(11):1052-4. DOI: 10.1056/NEJMe1109748. View