Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance
Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance
复制标题
2 型糖尿病患者循环 BMP™9 水平降低是胰岛素抵抗的标志
DOI：
10.1042/cs20160543
复制
发表时间：
2017-02-01
期刊：
影响因子：
6
通讯作者：
Zhang, Xianxiang
中科院分区：
文献类型：
--
作者：
Luo, Yong;Li, Ling;Zhang, Xianxiang
骨形态发生蛋白9 （BMP-9）已被证明可以改善糖尿病小鼠的葡萄糖稳态。然而，没有报告表明循环BMP-9水平与人类胰岛素抵抗（IR）或2型糖尿病（T2DM）之间的关系。本研究的目的是在横断面和介入性研究中探讨BMP-9与IR之间的关系。用酶联免疫吸附试验（ELISA）分析了280例特征明确的个体的循环BMP-9水平。对20名健康受试者进行2小时口服葡萄糖耐量试验（OGTT）和血糖-高胰岛素血症钳夹（EHC）。用脂质输注4 h诱导20例健康志愿者急性IR。采用Real-time (RT)-PCR和Western blotting检测BMP-9 mRNA和蛋白的表达情况。在为期24周的治疗试验中，研究了胰高血糖素样肽-1 （GLP-1）受体激动剂（PEX168）对循环BMP-9的影响。健康受试者的循环BMP-9水平明显高于新诊断的T2DM患者。循环BMP-9与HbA1c、空腹血糖（FBG）、OGTT、葡萄糖曲线下面积（AUC（葡萄糖））和胰岛素抵抗的稳态模型评估（HOMA-IR）呈负相关。多因素回归分析显示，BMP-9水平与非酯化脂肪酸（NEFA）和葡萄糖（AUC）独立相关。高胰岛素血症和脂质输注均降低循环BMP-9水平。2型糖尿病患者肌肉和脂肪组织中BMP-9 mRNA和蛋白表达明显降低。在安慰剂治疗组中，随着时间的推移，BMP-9水平持续下降，而在PEX 168治疗组中，BMP-9水平保持稳定。我们的数据表明，BMP-9可能在人类IR中发挥重要作用。
Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic-hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUC(glucose)) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUC(glucose). Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.