Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome

Ning Xu, David H. Geller, Michelle R. Jones, Vincent A. Funari, Ricardo Azziz, Mark O. Goodarzi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number57
Pages (from-to)99-104
Number of pages6
JournalJournal of Clinical and Translational Endocrinology
Volume2
Issue number3
DOIs
StatePublished - Jan 1 2015

Fingerprint

Polycystic Ovary Syndrome
Subcutaneous Fat
Insulin
Fasting
Genes
Phenotype
Gene Expression
Glucose
Metabolic Networks and Pathways
Androgens
Insulin Resistance
Testosterone
Real-Time Polymerase Chain Reaction
Signal Transduction
Body Mass Index
Homeostasis
Extremities

Keywords

  • Adipose tissue
  • Gene expression
  • Insulin signaling pathway
  • PCOS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome. / Xu, Ning; Geller, David H.; Jones, Michelle R.; Funari, Vincent A.; Azziz, Ricardo; Goodarzi, Mark O.

In: Journal of Clinical and Translational Endocrinology, Vol. 2, No. 3, 57, 01.01.2015, p. 99-104.

Research output: Contribution to journalArticle

Xu, Ning ; Geller, David H. ; Jones, Michelle R. ; Funari, Vincent A. ; Azziz, Ricardo ; Goodarzi, Mark O. / Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome. In: Journal of Clinical and Translational Endocrinology. 2015 ; Vol. 2, No. 3. pp. 99-104.
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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.

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