Insulin Resistance in Women with Polycystic Ovary Syndrome: Optimising treatment by Implementing an in vitro Insulin Resistance Organ Culture Model

Polycystic ovary syndrome (PCOS) affects about 5-10% of fertile women and is characterised by insulin resistance (IR), dyslipidaemia, hyperandrogenism, and oligomenorrhoe. The metabolic disruption in PCOS women requires treatment to prevent the progression of IR to diabetes and cardiovascular disease. Metformin is currently first line treatment for metabolic/glycemic abnormalities, but lacks beneficial effect on IR PCOS patients with side-effects and cost outweighing
benefits. Rosiglitazone has shown to reduce IR,but it was recently withdrawn from the market due to severe side-effects. Basic research into developing optimised drug treatments for IR in PCOS is critical to reducing the development of PCOS associated diabetes and cardiovascular disease. Testing and optimising drugs to reduce IR in PCOS patient samples is difficult due to ethical restrictions. In vitro organ culture models are valuable and reliable. Coronary arteries incubated with high doses of insulin and glucose will be screened for reliable intracellular IR associated biomarkers by western blot and real time PCR analysis. Vascular function by wire-myograph analysis will validate endothelial dysfunction and assess myocardial vascular injury associated responses. The associated response to clinically relevant anti-diabetic treatment options and adjunct therapy will be investigated. Developing a PCOS IR simulated organ culture model will enable us to understand the complicated intracellular signalling mechanisms leading to IR and may lead to development of potential new drug therapy options improving the PCOS IR treatment outcome.