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

Julie Lacombe, Omar Al Rifai, Lorraine Loter, Thomas Moran, Anne Frédérique Turcotte, Thomas Grenier-Larouche, André Tchernof, Laurent Biertho, André C. Carpentier, Denis Prud'homme, Rémi Rabasa-Lhoret, Gerard Karsenty, Claudia Gagnon, Weiping Jiang, Mathieu Ferron

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)E381-E391
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume318
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • Carboxylation
  • Diabetes
  • ELISA
  • Obesity
  • Osteocalcin
  • Uncarboxylated osteocalcin

Fingerprint

Dive into the research topics of 'Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function'. Together they form a unique fingerprint.

Cite this