Poster Presentation ANZOS-Breakthrough Discoveries Joint Annual Scientific Meeting 2018

Potential mechanisms of skeletal muscle insulin resistance in women with PCOS: a pilot study (#232)

Alba Moreno-Asso 1 , Luke C McIlvenna 1 , Rhiannon K Patten 1 , Nigel K Stepto 1
  1. Victoria University, Melbourne, Australia

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting metabolic, reproductive and mental health. It has a prevalence of 12-21% in Australian women and is associated with increased risk of insulin resistance (IR), gestational diabetes, early onset type 2 diabetes (T2D), cardiovascular disease, stroke and obesity. IR is present in 85% of women with PCOS and is mechanistically linked to dysfunctional skeletal muscle, a major contributor to whole body glucose uptake. However, unlike in other obesity related diseases, little is known about which molecular mechanisms in skeletal muscle contribute to the aetiology of PCOS. Transforming Growth Factor (TGFβ) ligand has been linked to an impaired improvement of skeletal muscle insulin sensitivity in T2D patients following an exercise intervention. Furthermore, TGFβ has also been associated with increased fibrosis in reproductive tissue of women with PCOS, predisposing them to metabolic and reproductive dysfunction. In this pilot study, we have investigated the effects of TGFβ and the Anti-Müllerian hormone (AMH), a novel TGFβ superfamily ligand elevated in serum of women with PCOS, on cultured myotubes from 20 overweight women with PCOS and 10 lean healthy controls, as a causal factor of skeletal muscle IR in PCOS. Our preliminary data show that the treatment with TGFβ and especially with high levels of AMH (30ng/ml) on myotubes from overweight women with PCOS negatively affects insulin signalling and glucose uptake via TGFβ signalling pathway compared to healthy lean controls. This suggests that these TGFβ superfamily ligands may play a role in the skeletal muscle IR in PCOS. These results contribute to a better understanding of the aetiology of IR in PCOS but still further investigation is warranted to determine how these factors interact with other clinical markers.