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Am J Physiol Endocrinol Metab. 2020 Mar 1;318(3):E381-E391. doi: 10.1152/ajpendo.00321.2019. Epub 2020 Jan 14.

Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function.

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Unité de Recherche en Physiologie Moléculaire, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada.
Department of Medicine, Université de Montréal, Québec, Canada.
BioLegend Incorporated, San Diego, California.
Center for Therapeutic Antibody Development, Icahn School of Medicine at Mount Sinai, New York, New York.
Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Center, Québec City, Québec, Canada.
Québec Heart and Lung Institute Research Centre, Québec City, Québec, Canada.
Service d'Endocrinologie, Département de Médecine, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, Québec, Canada.
School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
Institut du Savoir Montfort, Ottawa, Ontario, Canada.
Département de Nutrition, Université de Montréal, Montréal, Québec, Canada.
Unité de Recherche en Maladies Métaboliques, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada.
Department of Genetics and Development, Columbia University Medical Center, New York, New York.
Department of Medicine, Université Laval, Québec City, Québec, Canada.
Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.


Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes (n = 132), ucOCN correlated negatively with fasting glucose (r = -0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = -0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity (n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = -0.50, P = 0.046) and glycated hemoglobin (r = -0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp (P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.


ELISA; carboxylation; diabetes; obesity; osteocalcin; uncarboxylated osteocalcin


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