scholarly journals Dehydroepiandrosterone-induced activation of mTORC1 and inhibition of autophagy contribute to skeletal muscle insulin resistance in a mouse model of polycystic ovary syndrome

Oncotarget ◽  
2018 ◽  
Vol 9 (15) ◽  
pp. 11905-11921 ◽  
Author(s):  
Xi Song ◽  
Qiyang Shen ◽  
Liting Fan ◽  
Qiuxiao Yu ◽  
Xiao Jia ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

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.

Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo

2009 ◽  
Vol 418 (3) ◽  
pp. 665-671 ◽  
Author(s):  
Madhurima Rajkhowa ◽  
Sandra Brett ◽  
Daniel J. Cuthbertson ◽  
Christopher Lipina ◽  
Antonio J. Ruiz-Alcaraz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Insulin Signalling ◽  
Polycystic Ovary ◽  
Insulin Stimulation ◽  
Ovary Syndrome ◽  
Stimulation Of

Insulin resistance is a recognized feature of PCOS (polycystic ovary syndrome). However, the molecular reason(s) underlying this reduced cellular insulin sensitivity is not clear. The present study compares the major insulin signalling pathways in skeletal muscle isolated from PCOS and controls. We measured whole-body insulin sensitivity and insulin signalling in skeletal muscle biopsies taken before and after acute exposure to hyperinsulinaemia in nine women diagnosed with PCOS and seven controls. We examined the expression, basal activity and response to in vivo insulin stimulation of three signalling molecules within these human muscle samples, namely IRS-1 (insulin receptor substrate-1), PKB (protein kinase B) and ERK (extracellular-signal-regulated kinase) 1/2. There was no significant difference in the expression, basal activity or activation of IRS-1 or PKB between PCOS and control subjects. However, there was a severe attenuation of insulin stimulation of the ERK pathway in muscle from all but two of the women with PCOS (the two most obese), and an accompanying trend towards higher basal phosphorylation of ERK1/2 in PCOS. These results are striking in that the metabolic actions of insulin are widely believed to require the IRS-1/PKB pathway rather than ERK, and the former has been reported as defective in some previous PCOS studies. Most importantly, the molecular defect identified was independent of adiposity. The altered response of ERK to insulin in PCOS was the most obvious signalling defect associated with insulin resistance in muscle from these patients.

Acute exercise elicits differential expression of insulin resistance genes in the skeletal muscle of patients with polycystic ovary syndrome

2017 ◽  
Vol 86 (5) ◽  
pp. 688-697 ◽  
Author(s):  
Wagner Silva Dantas ◽  
Igor Hisashi Murai ◽  
Luiz Augusto Perandini ◽  
Hatylas Azevedo ◽  
Carlos Alberto Moreira-Filho ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Differential Expression ◽  
Resistance Genes ◽  
Acute Exercise ◽  
Polycystic Ovary ◽  
Ovary Syndrome

scholarly journals Molecular Mechanisms in Skeletal Muscle Underlying Insulin Resistance in Women Who Are Lean With Polycystic Ovary Syndrome

2018 ◽  
Vol 104 (5) ◽  
pp. 1841-1854 ◽  
Author(s):  
Solvejg L Hansen ◽  
Pernille F Svendsen ◽  
Jacob F Jeppesen ◽  
Louise D Hoeg ◽  
Nicoline R Andersen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Ovary Syndrome

scholarly journals Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome

2018 ◽  
Vol 103 (12) ◽  
pp. 4465-4477 ◽  
Author(s):  
Emma Nilsson ◽  
Anna Benrick ◽  
Milana Kokosar ◽  
Anna Krook ◽  
Eva Lindgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Dna Methylation ◽  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Differentially Expressed ◽  
Ovary Syndrome ◽  
Cpg Sites

Abstract Context Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index‒matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of ∼30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.

Oxidative stress markers in women with polycystic ovary syndrome without insulin resistance

2018 ◽  
Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Oxidative Stress Markers ◽  
Ovary Syndrome ◽  
Stress Markers
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