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 (AUCglucose) 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 AUCglucose. 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.
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Density-dependent scanning electron microscopy of calcifying vascular tissue (orange - calcification; green - collagen). Please see pp. 181-195 for more information. Image provided by Sergio Bertazzo.
Research Article|
January 18 2017
Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance
Yong Luo;
Yong Luo
1
*The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
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Ling Li;
Ling Li
1
†The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400010, China
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Xiaohui Xu;
Xiaohui Xu
1
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Tong Wu;
Tong Wu
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Mengliu Yang;
Mengliu Yang
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Cheng Zhang;
Cheng Zhang
*The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
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Huaming Mou;
Huaming Mou
*The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
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Tingting Zhou;
Tingting Zhou
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Yanjun Jia;
Yanjun Jia
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Chenrongrong Cai;
Chenrongrong Cai
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Hua Liu;
Hua Liu
§Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
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Gangyi Yang;
*The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
‡Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
Correspondence: Xianxiang Zhang (email [email protected]) or Gangyi Yang (email [email protected])
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Xianxiang Zhang
*The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
Correspondence: Xianxiang Zhang (email [email protected]) or Gangyi Yang (email [email protected])
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Publisher: Portland Press Ltd
Received:
July 18 2016
Revision Received:
November 26 2016
Accepted:
December 09 2016
Accepted Manuscript online:
December 09 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (3): 239–246.
Article history
Received:
July 18 2016
Revision Received:
November 26 2016
Accepted:
December 09 2016
Accepted Manuscript online:
December 09 2016
Citation
Yong Luo, Ling Li, Xiaohui Xu, Tong Wu, Mengliu Yang, Cheng Zhang, Huaming Mou, Tingting Zhou, Yanjun Jia, Chenrongrong Cai, Hua Liu, Gangyi Yang, Xianxiang Zhang; Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance. Clin Sci (Lond) 1 February 2017; 131 (3): 239–246. doi: https://doi.org/10.1042/CS20160543
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