Decreased circulating BMP-9 levels in patients with type 2 diabetes is a signature of IR

The objective of this study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analyzed by ELISA in 280 well-characterized individuals. 2-h oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp 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 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, OGTT, the area under the curve for glucose (AUCglucose) and HOMA-IR. Multivariate regression analyses showed that BMP-9 levels were independently associated with free fatty acid (FFA) and AUGglucose. Both hyperinsulinemia 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 160 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.

Source: Clinical Science - December 8, 2016 Category: Biomedical Science Authors: Luo, Y., Li, L., Xu, X., Wu, T., Yang, M., Zhang, C., Mou, H., Zhou, T., Jia, Y., Cai, C., Liu, H., Yang, G., Zhang, X. Tags: PublishAheadOfPrint Source Type: research