TY - JOUR
T1 - Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome
AU - Xu, Ning
AU - Geller, David H.
AU - Jones, Michelle R.
AU - Funari, Vincent A.
AU - Azziz, Ricardo
AU - Goodarzi, Mark O.
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015
Y1 - 2015
N2 - Abstract Objective Insulin resistance is a common feature of polycystic ovary syndrome (PCOS). The insulin signaling pathway consists of two major pathways, the metabolic and the mitogenic cascades. The many components of these pathways have not been comprehensively analyzed for differential expression in insulin-responsive tissues in PCOS. The goal of this study was to determine whether the core elements of the insulin signal transduction cascade were differentially expressed in subcutaneous adipose tissue (SAT) between PCOS and controls. Materials/methods Quantitative real-time PCR for 36 insulin signaling pathway genes was performed in subcutaneous adipose tissue from 22 white PCOS and 13 healthy controls. Results Genes in the insulin signaling pathway were not differentially expressed in subcutaneous adipose tissue between PCOS and controls (P 0.05 for all). Components mainly of the mitogenic pathway were correlated with both androgens and metabolic phenotypes. Expression levels of five genes (MKNK1, HRAS, NRAS, KRAS, and GSK3A) were positively correlated with total testosterone level (ρ > 0, P < 0.05). Inverse correlation was found between expression of six genes (HRAS, MAP2K2, NRAS, MAPK3, GRB2, and SHC1) and metabolic traits (body mass index, fasting glucose, fasting insulin, and HOMA-IR) (ρ < 0, P < 0.05). Conclusions Differential expression of core insulin signaling pathway components in subcutaneous adipose tissue is not a major contributor to the pathogenesis of PCOS. Correlation between clinical phenotypes and expression of several genes in the mitogenic limb of the insulin signaling pathway suggests mitogenic signaling by insulin may regulate steroidogenesis and glucose homeostasis.
AB - Abstract Objective Insulin resistance is a common feature of polycystic ovary syndrome (PCOS). The insulin signaling pathway consists of two major pathways, the metabolic and the mitogenic cascades. The many components of these pathways have not been comprehensively analyzed for differential expression in insulin-responsive tissues in PCOS. The goal of this study was to determine whether the core elements of the insulin signal transduction cascade were differentially expressed in subcutaneous adipose tissue (SAT) between PCOS and controls. Materials/methods Quantitative real-time PCR for 36 insulin signaling pathway genes was performed in subcutaneous adipose tissue from 22 white PCOS and 13 healthy controls. Results Genes in the insulin signaling pathway were not differentially expressed in subcutaneous adipose tissue between PCOS and controls (P 0.05 for all). Components mainly of the mitogenic pathway were correlated with both androgens and metabolic phenotypes. Expression levels of five genes (MKNK1, HRAS, NRAS, KRAS, and GSK3A) were positively correlated with total testosterone level (ρ > 0, P < 0.05). Inverse correlation was found between expression of six genes (HRAS, MAP2K2, NRAS, MAPK3, GRB2, and SHC1) and metabolic traits (body mass index, fasting glucose, fasting insulin, and HOMA-IR) (ρ < 0, P < 0.05). Conclusions Differential expression of core insulin signaling pathway components in subcutaneous adipose tissue is not a major contributor to the pathogenesis of PCOS. Correlation between clinical phenotypes and expression of several genes in the mitogenic limb of the insulin signaling pathway suggests mitogenic signaling by insulin may regulate steroidogenesis and glucose homeostasis.
KW - Adipose tissue
KW - Gene expression
KW - Insulin signaling pathway
KW - PCOS
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U2 - 10.1016/j.jcte.2015.06.002
DO - 10.1016/j.jcte.2015.06.002
M3 - Article
AN - SCOPUS:84937217866
SN - 2214-6237
VL - 2
SP - 99
EP - 104
JO - Journal of Clinical and Translational Endocrinology
JF - Journal of Clinical and Translational Endocrinology
IS - 3
M1 - 57
ER -