Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Early insulin signalling events in skeletal muscle from women with PCOS: impact of exercise (#62)

Nigel K Stepto 1 , Danielle Hiam 1 , Benedict J Canny 2 , Samantha Cassar 1 , Cherycer Harrison 3 , Anju Joham 3 , Rebecca Goldstein 3 , Samantha K Hutchison 3 , Juleen R Zierath 4 , Helena Teede 3
  1. Institute of Sport Exercise and Active Living, Victoria University, Melbourne, VIC, Australia
  2. Department of Physiology, Monash University, Clayton, VIC
  3. Monash Centre for Health Research Implementation, Monash University and Monash Health, Clayton, VIC, Australia
  4. Karolinska Institutet, Stockholm, Sweden

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy, affecting up to 1 in 5 young women. PCOS is a multifaceted disorder with metabolic and reproductive implications. Metabolic implications include obesity, insulin resistance, gestational diabetes, type 2 diabetes mellitus and risk factors for cardiovascular disease. Recently we have demonstrated that all women with PCOS have insulin resistance that cannot be explained by BMI or visceral fat alone (1). Furthermore, we have demonstrated that exercise training in PCOS enhances insulin sensitivity (2-3). While the mechanisms of insulin resistance in PCOS remain elusive, we hypothesised that the mechanisms responsible for the insulin resistance in PCOS may indeed be the early insulin signalling events in the skeletal muscle. Therefore , using euglycaemic hyperinsulinaemic clamp studies (1) and obtained muscle biopsies before and 40 minutes into the clamp to compare early insulin signalling events (immunoblotting) between lean and overweight women with and without PCOS (n=60), with a subset of the overweight women with and without PCOS (n=16) repeating the clamps and biopsies after 12 weeks of aerobic training. Here we show reduced responses in phosphorylation (normalised by prevailing insulin) of the insulin receptor (P<0.001), the p85 subunit of P-I3K (P<0.001), and serine phosphorylation of IRS-1 (P<0.001) and Akt (P<0.001) in PCOS are mediated by obesity women, however these defects were not normalised by exercise in overweight women with PCOS. These data provide mechanistic evidence for the synergism of obesity and PCOS on insulin sensitivity and that is only enhanced by exercise. Furthermore, intrinsic insulin levels found in lean women with PCOS resistance do not impact early insulin signalling events.

  1. Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod. 2013 Mar;28(3):777-84.
  2. Harrison CL, Stepto NK, Hutchison SK, Teede HJ. The impact of intensified exercise training on insulin resistance and fitness in overweight and obese women with and without polycystic ovary syndrome. Clin Endocrinol (Oxf). 2012 Mar;76(3):351-7.
  3. Hutchison SK, Stepto NK, Harrison CL, Moran LJ, Strauss BJ, Teede HJ. Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome. J Clin Endocrinol Metab. 2011 Jan;96(1):E48-56.