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Nutrients 2018, 10(7), 847; https://doi.org/10.3390/nu10070847

Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity

1
Institute of Health and Sport, Victoria University, Melbourne, VIC 8011, Australia
2
Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, NSW 2006, Australia
3
Australian Institute for Musculoskeletal Science, Department of Medicine, Western Health, Melbourne Medical School, University of Melbourne, Melbourne, VIC 3021, Australia
4
The Medical School, University of Western Australia, Perth, WA 6009, Australia
5
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA 6150, Australia
*
Authors to whom correspondence should be addressed.
Received: 7 June 2018 / Revised: 22 June 2018 / Accepted: 25 June 2018 / Published: 29 June 2018
(This article belongs to the Special Issue Vitamin K in Human Health and Disease)
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Abstract

Recent advances have indicated that osteocalcin, and in particular its undercarboxylated form (ucOC), is not only a nutritional biomarker reflective of vitamin K status and an indicator of bone health but also an active hormone that mediates glucose metabolism in experimental studies. This work has been supported by the putative identification of G protein-coupled receptor, class C, group 6, member A (GPRC6A) as a cell surface receptor for ucOC. Of note, ucOC has been associated with diabetes and with cardiovascular risk in epidemiological studies, consistent with a pathophysiological role for ucOC in vivo. Limitations of existing knowledge include uncertainty regarding the underlying mechanisms by which ucOC interacts with GPRC6A to modulate metabolic and cardiovascular outcomes, technical issues with commonly used assays for ucOC in serum, and a paucity of clinical trials to prove causation and illuminate the scope for novel health interventions. A key emerging area of research is the role of ucOC in relation to expression of GPRC6A in muscle, and whether exercise interventions may modulate metabolic outcomes favorably in part via ucOC. Further research is warranted to clarify potential direct and indirect roles for ucOC in human health and cardiometabolic diseases. View Full-Text
Keywords: osteocalcin; undercarboxylated osteocalcin; GPRC6A; insulin resistance; diabetes; cardiovascular disease; bone; muscle osteocalcin; undercarboxylated osteocalcin; GPRC6A; insulin resistance; diabetes; cardiovascular disease; bone; muscle
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Lin, X.; Brennan-Speranza, T.C.; Levinger, I.; Yeap, B.B. Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity. Nutrients 2018, 10, 847.

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