Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes
Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes
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DOI：
10.1186/s13098-020-00579-3
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发表时间：
2020-08-17
影响因子：
4.8
通讯作者：
Fujimoto, Shimpei
中科院分区：
文献类型：
--
作者：
Funakoshi, Shogo;Yoshimura, Kumiko;Fujimoto, Shimpei
低羧化骨钙素（Undercarboxylated ostecalcin, ucOC）是一种由成骨细胞产生的分泌蛋白，可调节啮齿动物的胰岛素分泌和胰岛素敏感性。然而，这些作用对人体葡萄糖代谢的意义尚不清楚。此外，ucOC在不同程度的葡萄糖耐受不良（包括糖尿病）中的病理生理作用有待阐明。本研究分析了正常糖耐量（NGT）组、糖代谢受损（IGM）组和糖尿病（DM）组ucOC与胰岛素分泌及敏感性指标的相关性。方法根据未服用糖尿病药物或可能影响ucOC水平的药物的日本个体的75 g OGTT数据，将个体分为糖耐量正常（NGT）、糖代谢受损（IGM）或糖尿病（DM）。每组连续招募25人[共75人，年龄：65 +/- 11 (mean +/- SD)；BMI: 24.9 +/- 3.8 kg/m[2]。计算QUICKI和Matsuda指数（MI）作为胰岛素敏感性指标。计算稳态模型评估（HOMA - β）和胰岛素生成指数（IGI）作为胰岛素分泌指标。UcOC采用ECLIA测定。ucOC、HOMA-beta、IGI和MI采用正态分布对数(e)变换（ln-）值。结果三组间ucOC差异无统计学意义。多元回归分析结果显示，在三组中，ln-ucOC与年龄、性别、BMI、腰围、空腹血糖、葡萄糖负荷后120分钟的血糖、空腹血浆免疫反应性胰岛素、ln- homa - β、QUICKI或ln-MI均无显著相关。有趣的是，ln-ucOC仅在DM组与ln-IGI （r = 0.422,P = 0.0354）和HbA1c （r = - 0.574,P = 0.0027）相关。在DM组中，ln-IGI与年龄、性别、BMI或HbA1c无显著相关性。多元回归分析结果显示，DM组BMI （β = 0.598, P = 0.0014）和ln-ucOC （β = 0.641, P = 0.0007）能够独立预测ln-IGI （R-2 = 0.488,P = 0.0006）。结论在我们的研究中，ucOC与日本糖尿病患者的胰岛素分泌呈正相关，独立于BMI。这些结果表明，ucOC在糖尿病患者的胰岛素分泌中比在胰岛素敏感性中发挥更重要的作用。
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)-beta 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-beta, 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-beta, 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 (beta = 0.598, P = 0.0014) and ln-ucOC (beta = 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.