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

Gynecol Endocrinol. 2022 Sep;38(9):781-789. doi: 10.1080/09513590.2022.2109144. Epub 2022 Aug 11.

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.

Keywords: Bone morphogenetic protein-9; insulin resistance; polycystic ovary syndrome; 多囊卵巢综合征; 胰岛素抵抗; 骨形态发生蛋白-9.

MeSH terms

  • Animals
  • Exenatide
  • Female
  • Glucose
  • Growth Differentiation Factor 2
  • Humans
  • Insulin
  • Insulin Resistance*
  • Phosphatidylinositol 3-Kinases
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Receptors, Androgen

Substances

  • Growth Differentiation Factor 2
  • Insulin
  • Receptors, Androgen
  • Exenatide
  • Proto-Oncogene Proteins c-akt
  • Glucose