Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes

Abstract

Background: Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts that regulates insulin secretion and insulin sensitivity in rodents. However, the significance of these effects on glucose metabolism in human remains unknown. Moreover, the pathophysiological roles of ucOC on varying degrees of glucose intolerance, including diabetes need to be elucidated. In the present study, correlations between ucOC and indices of insulin secretion and sensitivity were analyzed in normal glucose tolerance (NGT), impaired glucose metabolism (IGM), and diabetes mellitus (DM) groups. Methods: Based on 75 g OGTT data in Japanese individuals without diabetic medication, or medications which may affect ucOC levels, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m 2 ]. QUICKI and Matsuda index (MI) were calculated as insulin sensitivity indices. Homeostasis model assessment (HOMA)-β and insulinogenic index (IGI) were calculated as insulin secretion indices. UcOC was measured using ECLIA. Normally-distributed log e-transformed (ln-) values were used for ucOC, HOMA-β, IGI, and MI. Results: The ucOC was not significantly different among the three groups. The results of multiple regression analysis showed that ln-ucOC did not significantly correlate with age, sex, BMI, waist circumference, fasting plasma glucose, plasma glucose 120 min after glucose loading, fasting plasma immunoreactive insulin, ln-HOMA-β, QUICKI, or ln-MI in any of the three groups. Interestingly, ln-ucOC correlated with ln-IGI (r = 0.422, P = 0.0354) and HbA1c (r = − 0.574, P = 0.0027) only in the DM group. There was no significant correlation between ln-IGI and age, sex, BMI, or HbA1c in the DM group. Further, the results of multiple regression analysis showed that ln-IGI could be independently predicted by BMI (β = 0.598, P = 0.0014) and ln-ucOC (β = 0.641, P = 0.0007) in the DM group (R 2 = 0.488, P = 0.0006). Conclusion: In our study, ucOC positively correlated with insulin secretion independently of BMI in Japanese individuals with diabetes. These results suggest that ucOC plays more important roles in insulin secretion than in insulin sensitivity in individuals with diabetes.

Does Serum Osteocalcin Level Affect Carotid Atherosclerosis in Post-Menopausal Diabetic Females? A Case-Control Study

“…39 Similar results were obtained in Japanese individuals with diabetes. 40 Interestingly, in our study OCN was not correlated with BMI and multivariate regression showed that OCN was only significantly and negatively associated with FBG and s.insulin. These results suggest that OCN might have an important effect on insulin secretion than on insulin sensitivity in diabetic individuals.…”

Association between Serum Osteocalcin Levels and Metabolic Syndrome according to the Menopausal Status of Korean Women

“… 11 53 54 However, it is still unclear whether undercarboxylated osteocalcin is the metabolically active form in humans. 8 9 10 11 12 13 We defined perimenopausal women by FSH levels while studying subgroup analysis considering menopausal transition. 26 Application of other criteria for perimenopause may yield different results.…”

“…Although the undercarboxylated form of osteocalcin enhanced pancreatic β-cell proliferation and insulin secretion in human pancreatic islets in vitro, 7 the significance of these effects on glucose metabolism in vivo in humans remains unknown. 8 9 10 11 12 13 On the other hand, in several clinical studies, serum osteocalcin was correlated with insulin resistance and appeared to be involved in the development of obesity and diabetes mellitus. 10 13 14 Accumulating evidence points to an association between serum osteocalcin levels and development of MetS in men as well as in postmenopausal women.…”

Low Serum Osteocalcin Level as a Risk Factor for Metabolic Syndrome in Korean Men: A Retrospective Longitudinal Study

“…Second, we did not consider dietary or exercise habits, which are well-known effective factors for the development or resolution of MetS. Third, whether or not undercarboxylated osteocalcin is the active form in humans remains unclear [27,28,52,53]. Undercarboxylated osteocalcin alone has a biological effect in mice [6].…”