You-Cheol Hwang1, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung. 1. Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee East-West Neo Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
Abstract
BACKGROUND: Recent human studies support the notion that serum osteocalcin increases beta-cell proliferation and insulin secretion, and improves insulin sensitivity. However, no study has examined the effects of serum osteocalcin gamma-carboxylation status on these associations or determined the role of uncarboxylated osteocalcin in glucose metabolism in humans. METHODS: The aim of this study was to determine the association between uncarboxylated osteocalcin and beta-cell function and insulin sensitivity in humans. As many as 199 men, aged 25-60 years (mean age, 47 years), who had never been treated with glucose lowering agents, were enrolled in this cross-sectional study. OGTT was performed and other metabolic parameters, such as, BMI, BP, lipid profiles, and both uncarboxylated and carboxylated osteocalcin plasma levels were measured. RESULTS: When subjects were divided into tertiles by uncarboxylated and carboxylated osteocalcin plasma concentrations, subjects in the upper tertile of each showed lower fasting and post-challenge glucose levels after adjusting for age and BMI (P < 0.05). The upper uncarboxylated osteocalcin tertile was associated with higher HOMA-B% levels, which are representative of beta-cell function (P < 0.05), and the upper carboxylated osteocalcin tertile was associated with lower HOMA-IR values, which are representative of insulin resistance (P < 0.05). CONCLUSIONS: Elevated levels of both carboxylated and uncarboxylated forms of osteocalcin were associated with improved glucose tolerance. Moreover, the uncarboxylated form of osteocalcin was found to be associated with enhanced beta-cell function, and the carboxylated form was associated with improved insulin sensitivity in middle-aged male subjects.
BACKGROUND: Recent human studies support the notion that serum osteocalcin increases beta-cell proliferation and insulin secretion, and improves insulin sensitivity. However, no study has examined the effects of serum osteocalcin gamma-carboxylation status on these associations or determined the role of uncarboxylated osteocalcin in glucose metabolism in humans. METHODS: The aim of this study was to determine the association between uncarboxylated osteocalcin and beta-cell function and insulin sensitivity in humans. As many as 199 men, aged 25-60 years (mean age, 47 years), who had never been treated with glucose lowering agents, were enrolled in this cross-sectional study. OGTT was performed and other metabolic parameters, such as, BMI, BP, lipid profiles, and both uncarboxylated and carboxylated osteocalcin plasma levels were measured. RESULTS: When subjects were divided into tertiles by uncarboxylated and carboxylated osteocalcin plasma concentrations, subjects in the upper tertile of each showed lower fasting and post-challenge glucose levels after adjusting for age and BMI (P < 0.05). The upper uncarboxylated osteocalcin tertile was associated with higher HOMA-B% levels, which are representative of beta-cell function (P < 0.05), and the upper carboxylated osteocalcin tertile was associated with lower HOMA-IR values, which are representative of insulin resistance (P < 0.05). CONCLUSIONS: Elevated levels of both carboxylated and uncarboxylated forms of osteocalcin were associated with improved glucose tolerance. Moreover, the uncarboxylated form of osteocalcin was found to be associated with enhanced beta-cell function, and the carboxylated form was associated with improved insulin sensitivity in middle-aged male subjects.
Authors: A L Kuipers; C Gundberg; C M Kammerer; A S Dressen; C S Nestlerode; A L Patrick; V W Wheeler; C H Bunker; A B Newman; J M Zmuda Journal: Osteoporos Int Date: 2011-09-21 Impact factor: 4.507
Authors: Claudia Boucher-Berry; Phyllis W Speiser; Dennis E Carey; Steven P Shelov; Siham Accacha; Ilene Fennoy; Robert Rapaport; Yomery Espinal; Michael Rosenbaum Journal: J Bone Miner Res Date: 2012-02 Impact factor: 6.741
Authors: Barbara A Gower; Norman K Pollock; Krista Casazza; Thomas L Clemens; Laura Lee Goree; Wesley M Granger Journal: J Clin Endocrinol Metab Date: 2013-04-24 Impact factor: 5.958