Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome
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 i...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-09-01
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| Series: | Journal of Clinical & Translational Endocrinology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214623715000587 |
| _version_ | 1818113941983723520 |
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| author | Ning Xu David H. Geller Michelle R. Jones Vincent A. Funari Ricardo Azziz Mark O. Goodarzi |
| author_facet | Ning Xu David H. Geller Michelle R. Jones Vincent A. Funari Ricardo Azziz Mark O. Goodarzi |
| author_sort | Ning Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T03:42:50Z |
| format | Article |
| id | doaj.art-62bc4456f9554d2b82ff2c4223433c45 |
| institution | Directory Open Access Journal |
| issn | 2214-6237 |
| language | English |
| last_indexed | 2024-12-11T03:42:50Z |
| publishDate | 2015-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Clinical & Translational Endocrinology |
| spelling | doaj.art-62bc4456f9554d2b82ff2c4223433c452022-12-22T01:22:05ZengElsevierJournal of Clinical & Translational Endocrinology2214-62372015-09-01239910410.1016/j.jcte.2015.06.002Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndromeNing Xu0David H. Geller1Michelle R. Jones2Vincent A. Funari3Ricardo Azziz4Mark O. Goodarzi5Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Obstetrics and Gynecology, Georgia Regents University, Augusta, GA 30901, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAObjective: 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.http://www.sciencedirect.com/science/article/pii/S2214623715000587PCOSInsulin signaling pathwayGene expressionAdipose tissue |
| spellingShingle | Ning Xu David H. Geller Michelle R. Jones Vincent A. Funari Ricardo Azziz Mark O. Goodarzi Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome Journal of Clinical & Translational Endocrinology PCOS Insulin signaling pathway Gene expression Adipose tissue |
| title | Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome |
| title_full | Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome |
| title_fullStr | Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome |
| title_full_unstemmed | Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome |
| title_short | Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome |
| title_sort | comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome |
| topic | PCOS Insulin signaling pathway Gene expression Adipose tissue |
| url | http://www.sciencedirect.com/science/article/pii/S2214623715000587 |
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