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

2020 ◽  
Author(s):  
Ada Admin ◽  
Solvejg L. Hansen ◽  
Kirstine N. Bojsen-Møller ◽  
Anne-Marie Lundsgaard ◽  
Frederikke L. Hendrich ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Ovary Syndrome ◽  
Leg Blood Flow

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.

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

2020 ◽  
Author(s):  
Ada Admin ◽  
Solvejg L. Hansen ◽  
Kirstine N. Bojsen-Møller ◽  
Anne-Marie Lundsgaard ◽  
Frederikke L. Hendrich ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Ovary Syndrome ◽  
Leg Blood Flow

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.

scholarly journals Electroacupuncture Mimics Exercise-Induced Changes in Skeletal Muscle Gene Expression in Women With Polycystic Ovary Syndrome

2020 ◽  
Vol 105 (6) ◽  
pp. 2027-2041 ◽  
Author(s):  
Anna Benrick ◽  
Nicolas J Pillon ◽  
Emma Nilsson ◽  
Eva Lindgren ◽  
Anna Krook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Ovary Syndrome ◽  
Altered Expression

Abstract Context Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown. Objective To identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS). Design/Participants In a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays. Results A single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q < 0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q < 0.20), and these changes correlated with altered expression of 101 genes (P < 0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these 2 genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis. Conclusion Our findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition

2013 ◽  
Vol 126 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Victoria S. Sprung ◽  
Helen Jones ◽  
Christopher J. A. Pugh ◽  
Nabil F. Aziz ◽  
Christina Daousi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Disease Risk ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Alcoholic Fatty Liver

PCOS (polycystic ovary syndrome) is associated with IR (insulin resistance), increased visceral fat and NAFLD (non-alcoholic fatty liver disease) all of which may contribute to endothelial dysfunction, an early marker of CVD (cardiovascular disease) risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of AT (adipose tissue) compartments and the size of intracellular TAG (triacylglycerol) pools in liver and skeletal muscle. A total of 19 women with PCOS (means±S.D.; 26±6 years, 36±5 kg/m2) and 16 control women (31±8 years, 30±6 kg/m2) were recruited. Endothelial function was assessed in the brachial artery using FMD (flow-mediated dilation). VAT (visceral AT) and abdominal SAT (subcutaneous AT) volume were determined by whole body MRI, and liver and skeletal muscle TAG by 1H-MRS (proton magnetic resonance spectroscopy). Cardiorespiratory fitness and HOMA-IR (homoeostasis model assessment of IR) were also determined. Differences between groups were analysed using independent Student's t tests and ANCOVA (analysis of co-variance). FMD was impaired in PCOS by 4.6% [95% CI (confidence interval), 3.0–7.7; P<0.001], and this difference decreased only slightly to 4.2% (95% CI, 2.4–6.1; P<0.001) when FMD was adjusted for individual differences in visceral and SAT and HOMA-IR. This magnitude of impairment was also similar in lean and obese PCOS women. The results suggest that endothelial dysfunction in PCOS is not explained by body fat distribution or volume. FMD might be a useful independent prognostic tool to assess CVD risk in this population.

Acupuncture increases whole body glucose uptake during and after stimulation in women with polycystic ovary syndrome

2014 ◽  
Vol 102 (3) ◽  
pp. e29 ◽  
Author(s):  
E. Stener-Victorin ◽  
A. Benrick ◽  
M. Kokosar ◽  
M. Maliqueo ◽  
C. Behre ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Ovary Syndrome

scholarly journals Maternal Overweight vs. Polycystic Ovary Syndrome: Disentangling Their Impact on Insulin Action in Pregnancy—A Prospective Study

2020 ◽  
Vol 10 (1) ◽  
pp. 35
Author(s):  
Michael Feichtinger ◽  
Tina Linder ◽  
Ingo Rosicky ◽  
Daniel Eppel ◽  
Christian Schatten ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Polycystic Ovary Syndrome ◽  
Insulin Action ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Whole Body ◽  
Ovary Syndrome ◽  
A Prospective Study ◽  
Maternal Overweight

Background: To investigate insulin sensitivity and glucose metabolism in pregnant lean and overweight polycystic ovary syndrome (PCOS) patients vs. lean and overweight controls without PCOS. Methods: Prospective cohort study on 67 pregnant women (31 with PCOS and 36 controls, subdivided into overweight or obese and normal weight). All women underwent a 2h-OGTT including glucose, insulin, and C-peptide in early- and mid-gestation and were followed-up until delivery. Results: Insulin sensitivity and glucometabolic parameters were comparable between PCOS patients and controls, whereas marked differences were observed between overweight/obese and lean mothers. Impaired whole-body insulin sensitivity at early pregnancy is mainly a consequence of higher BMI (body mass index; p < 0.001) compared to PCOS (p = 0.216), whereby no interaction between overweight/obesity and PCOS was observed (p = 0.194). Moreover, overweight was significantly associated with gestational diabetes (p = 0.0003), whereas there were no differences between women with and without PCOS (p = 0.51). Birth weight was inversely related to whole-body insulin sensitivity (rho = −0.33, p = 0.014) and positively associated with higher pregestational BMI (rho = 0.33, p = 0.012), whereas there was no association with PCOS. Conclusions: Impaired insulin action was mainly a consequence of overweight rather than PCOS. Our data suggest that overweight is more relevant than PCOS for the effects on insulin sensitivity and impaired glucose metabolism.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

cGMP phosphodiesterase inhibition improves the vascular and metabolic actions of insulin in skeletal muscle

2011 ◽  
Vol 301 (2) ◽  
pp. E342-E350 ◽  
Author(s):  
A. J. Genders ◽  
E. A. Bradley ◽  
S. Rattigan ◽  
S. M. Richards
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Mrna Level ◽  
Microvascular Perfusion ◽  
Microvascular Blood Flow ◽  
Whole Body ◽  
Acute Administration ◽  
Dependent Inhibition ◽  
Promising Avenue

There is considerable support for the concept that insulin-mediated increases in microvascular blood flow to muscle impact significantly on muscle glucose uptake. Since the microvascular blood flow increases with insulin have been shown to be nitric oxide-dependent inhibition of cGMP-degrading phosphodiesterases (cGMP PDEs) is predicted to enhance insulin-mediated increases in microvascular perfusion and muscle glucose uptake. Therefore, we studied the effects of the pan-cGMP PDE inhibitor zaprinast on the metabolic and vascular actions of insulin in muscle. Hyperinsulinemic euglycemic clamps (3 mU·min−1·kg−1) were performed in anesthetized rats and changes in microvascular blood flow assessed from rates of 1-methylxanthine metabolism across the muscle bed by capillary xanthine oxidase in response to insulin and zaprinast. We also characterized cGMP PDE isoform expression in muscle by real-time PCR and immunostaining of frozen muscle sections. Zaprinast enhanced insulin-mediated microvascular perfusion by 29% and muscle glucose uptake by 89%, while whole body glucose infusion rate during insulin infusion was increased by 33% at 2 h. PDE2, -9, and -10 were the major isoforms expressed at the mRNA level in muscle, while PDE1B, -9A, -10A, and -11A proteins were expressed in blood vessels. Acute administration of the cGMP PDE inhibitor zaprinast enhances muscle microvascular blood flow and glucose uptake response to insulin. The expression of a number of cGMP PDE isoforms in skeletal muscle suggests that targeting specific cGMP PDE isoforms may provide a promising avenue for development of a novel class of therapeutics for enhancing muscle insulin sensitivity.

scholarly journals Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

2014 ◽  
Vol 171 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Alessandra Gambineri ◽  
Flaminia Fanelli ◽  
Federica Tomassoni ◽  
Alessandra Munarini ◽  
Uberto Pagotto ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
Whole Body ◽  
Mrna Levels ◽  
Ovary Syndrome ◽  
Tissue Specific ◽  
Cortisol Metabolism ◽  
Cortisol Metabolites

ContextAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic–pituitary–adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.ObjectiveTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.DesignCase–control study.SettingMedical center.PatientsA total of 20 overweight–obese unmedicated Caucasian women with PCOS, aged 18–45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, andHSD11B1genotypes (rs846910 and rs12086634).Main outcome measuresCortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[2H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-2H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity andHSD11B1mRNA were measured,ex vivo, in biopsies.ResultsUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissueHSD11B1mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.ConclusionsTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.

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