American Diabetes Association
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Mechanisms underlying absent training-induced improvement in insulin action in lean, hyperandrogenic women with polycystic ovary syndrome (PCOS)

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posted on 2020-09-04, 07:29 authored by Ada AdminAda Admin, Solvejg L. Hansen, Kirstine N. Bojsen-Møller, Anne-Marie Lundsgaard, Frederikke L. Hendrich, Lisbeth Nilas, Kim A. Sjøberg, Janne R. Hingst, Annette K. Serup, Carlos Henríquez-Olguín, Christian S. Carl, Louise F. Wernblad, Marie Henneberg, Katja M. Lustrup, Christine Hansen, Thomas E. Jensen, Sten Madsbad, Jørgen F.P. Wojtaszewski, Erik A. Richter, Bente Kiens
Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle improving glucose uptake and metabolism in both healthy and type 2 diabetic individuals. In the present study, lean, hyperandrogenic women with PCOS (n=9) and healthy controls (CON, n=9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole body insulin action by 26% and insulin-stimulated leg glucose uptake by 53%, together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in maximal oxygen uptake. In skeletal muscle of CON, but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose handling proteins for insulin-stimulated glucose uptake in skeletal muscle, and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.

Funding

The study was supported by The Novo-Nordisk Research Foundation. The University of Copenhagen Excellence Program for Interdisciplinary Research (2016) “Physical Activity and Nutrition for Improvement of Health”. Anne-Marie Lundsgaard was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant number NNF17SA0031406. K.A.S. was supported by a postdoctoral research grant from the Council for Independent Research/ Medicine grant number 4092-00309.

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