Bone morphogenetic protein-9 maybe an important factor which improves insulin resistance in PCOS

Abstract

Background

Polycystic ovary syndrome (PCOS) is closely related to insulin resistance (IR). Bone morphogenetic protein-9 (BMP-9) plays an important role in maintaining glucose homeostasis, but an association between BMP-9 and PCOS has not been reported. Here, we report the changes in BMP-9 and the influence of this protein on IR in PCOS.

Methods

57 PCOS patients were selected (among them 25 received interventional treatment with exenatide (EX) for 3 months, and 32 received no treatment). 22 normal control individuals and 30 IR patients were also recruited. We evaluated IR with the euglycaemic-hyperinsulinaemic clamp (EHC) technique. IR and the glucose metabolism rate were assessed by EHC and [3-3H]glucose tracer experiments. We determined the protein expression levels of BMP-9, p-AKT (protein kinase B) and androgen receptor in the ovaries and liver by Western blotting.

Results

We found that circulating BMP-9 levels were significantly decreased in PCOS with IR patients. Circulating BMP-9 levels and p-AKT levels were decreased in HFD and PCOS rats and increased after MF and EX treatment. The glucose infusion rate, glucose disappearance rate and suppression of hepatic glucose production decreased in the HFD and PCOS groups, the opposite results were found for HGP. AR protein expression levels increased in the HFD and PCOS groups and decreased in the MF and EX groups.

Conclusions

Our study results suggest that BMP-9 is an independent factor that influences IR in PCOS patients. The decrease in BMP-9 levels in the liver and ovaries may be involved in IR through the PI3K/AKT signaling pathway in PCOS rats.

摘要

目的

多囊卵巢综合征(PCOS)与胰岛素抵抗(IR)密切相关。骨形态发生蛋白-9 (BMP-9)在维持葡萄糖稳态中发挥重要作用, 但BMP-9与多囊症之间的联系尚未报道。本文报道了多囊卵巢综合征中BMP-9的变化及其对IR的影响。

方法

多囊卵巢综合征(PCOS)与胰岛素抵抗(IR)密切相关。骨形态发生蛋白-9 (BMP-9)在维持葡萄糖稳态中发挥重要作用, 但BMP-9与多囊症之间的联系尚未报道。本文报道了多囊卵巢综合征中BMP-9的变化及其对IR的影响。

结果

我们发现, 在多囊卵巢综合征合并IR患者中, 循环BMP-9水平显著降低。HFD和PCOS大鼠循环BMP-9和p-AKT水平降低, MF和EX处理后升高。HFD和PCOS组的葡萄糖输注率、葡萄糖消失率和对肝脏葡萄糖生成的抑制均降低, HGP组则相反。AR蛋白表达水平在HFD和PCOS组升高, 在MF和EX组降低。

结论

我们的研究结果表明BMP-9是影响多囊卵巢综合征患者IR的独立因素。PCOS大鼠肝脏和卵巢BMP-9水平的降低可能通过PI3K/AKT信号通路参与IR。

缩写

PCOS:多囊卵巢综合征;IR:胰岛素抵抗;BMP-9:骨形态发生蛋白-9;GDF-2:生长分化因子2;OGTT:口服葡萄糖耐量试验;EHC:高血糖高胰岛素钳夹;BMI:身体质量指数;EX:艾塞那肽;WC:腰围;WHR:腰臀比;OGIRT:口服葡萄糖胰岛素释放试验;GIR:葡萄糖输液速率;GlP-1: 胰高血糖素样肽-1;HbA1c:糖化血红蛋白;SPF:特定的无菌;HFD:高脂肪饮食;DHEA:脱氢表雄酮;ND:正常饮食;MF:二甲双胍;GTTs:葡萄糖耐量试验;ITTs:胰岛素耐受性试验;GRa:葡萄糖出现率;GRd:葡萄糖清除率(消失率);HGP:肝脏葡萄糖生成;SUPP-HGP:HGP抑制;IHC:免疫组织化学;AR:雄激素受体。

Keywords:

• Bone morphogenetic protein-9
• polycystic ovary syndrome
• insulin resistance

关键词:

• 骨形态发生蛋白-9
• 多囊卵巢综合征
• 胰岛素抵抗

Acknowledgements

The authors wish to thank all the individuals who helped throughout the study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by the National Natural Science Foundation of China (grant no. 82060273) and Youth Science and Technology Talent Development Project of Guizhou Education Department, KY[2018] No. 237.