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miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance

Approximately 70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR) above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT). In AT, analysis of the IRS/PI3-K/AKT pathway signaling components identified onl...

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Autores principales: Chen, Yen-Hao, Heneidi, Saleh, Lee, Jung-Min, Layman, Lawrence C., Stepp, David W., Gamboa, Gloria Mabel, Chen, Bo-Shiun, Chazenbalk, Gregorio, Azziz, Ricardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712080/
https://www.ncbi.nlm.nih.gov/pubmed/23493574
http://dx.doi.org/10.2337/db12-0963
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author Chen, Yen-Hao
Heneidi, Saleh
Lee, Jung-Min
Layman, Lawrence C.
Stepp, David W.
Gamboa, Gloria Mabel
Chen, Bo-Shiun
Chazenbalk, Gregorio
Azziz, Ricardo
author_facet Chen, Yen-Hao
Heneidi, Saleh
Lee, Jung-Min
Layman, Lawrence C.
Stepp, David W.
Gamboa, Gloria Mabel
Chen, Bo-Shiun
Chazenbalk, Gregorio
Azziz, Ricardo
author_sort Chen, Yen-Hao
collection PubMed
description Approximately 70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR) above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT). In AT, analysis of the IRS/PI3-K/AKT pathway signaling components identified only GLUT4 expression to be significantly lower in PCOS patients and in control subjects with IR. We examined the role of miRNAs, particularly in the regulation of GLUT4, the insulin-sensitive glucose transporter, in the AT of PCOS and matched control subjects. PCOS AT was determined to have a differentially expressed miRNA profile, including upregulated miR-93, -133, and -223. GLUT4 is a highly predicted target for miR-93, while miR-133 and miR-223 have been demonstrated to regulate GLUT4 expression in cardiomyocytes. Expression of miR-93 revealed a strong correlation between the homeostasis model assessment of IR in vivo values and GLUT4 and miR-93 but not miR-133 and -223 expression in human AT. Overexpression of miR-93 resulted in downregulation of GLUT4 gene expression in adipocytes through direct targeting of the GLUT4 3′UTR, while inhibition of miR-93 activity led to increased GLUT4 expression. These results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93 and demonstrate upregulated miR-93 expression in all PCOS, and in non-PCOS women with IR, possibly accounting for the IR of the syndrome. In contrast, miR-133 and miR-223 may have a different, although yet to be defined, role in the IR of PCOS.
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spelling pubmed-37120802014-07-01 miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance Chen, Yen-Hao Heneidi, Saleh Lee, Jung-Min Layman, Lawrence C. Stepp, David W. Gamboa, Gloria Mabel Chen, Bo-Shiun Chazenbalk, Gregorio Azziz, Ricardo Diabetes Original Research Approximately 70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR) above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT). In AT, analysis of the IRS/PI3-K/AKT pathway signaling components identified only GLUT4 expression to be significantly lower in PCOS patients and in control subjects with IR. We examined the role of miRNAs, particularly in the regulation of GLUT4, the insulin-sensitive glucose transporter, in the AT of PCOS and matched control subjects. PCOS AT was determined to have a differentially expressed miRNA profile, including upregulated miR-93, -133, and -223. GLUT4 is a highly predicted target for miR-93, while miR-133 and miR-223 have been demonstrated to regulate GLUT4 expression in cardiomyocytes. Expression of miR-93 revealed a strong correlation between the homeostasis model assessment of IR in vivo values and GLUT4 and miR-93 but not miR-133 and -223 expression in human AT. Overexpression of miR-93 resulted in downregulation of GLUT4 gene expression in adipocytes through direct targeting of the GLUT4 3′UTR, while inhibition of miR-93 activity led to increased GLUT4 expression. These results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93 and demonstrate upregulated miR-93 expression in all PCOS, and in non-PCOS women with IR, possibly accounting for the IR of the syndrome. In contrast, miR-133 and miR-223 may have a different, although yet to be defined, role in the IR of PCOS. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712080/ /pubmed/23493574 http://dx.doi.org/10.2337/db12-0963 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Chen, Yen-Hao
Heneidi, Saleh
Lee, Jung-Min
Layman, Lawrence C.
Stepp, David W.
Gamboa, Gloria Mabel
Chen, Bo-Shiun
Chazenbalk, Gregorio
Azziz, Ricardo
miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
title miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
title_full miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
title_fullStr miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
title_full_unstemmed miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
title_short miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
title_sort mirna-93 inhibits glut4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712080/
https://www.ncbi.nlm.nih.gov/pubmed/23493574
http://dx.doi.org/10.2337/db12-0963
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