miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance.

Yen Hao Chen, Saleh Heneidi, Jung Min Lee, Lawrence C. Layman, David W. Stepp, Gloria Mabel Gamboa, Bo Shiun Chen, Gregorio Chazenbalk, Ricardo Azziz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2278-2286
Number of pages9
JournalDiabetes
Volume62
Issue number7
StatePublished - Jul 1 2013

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Polycystic Ovary Syndrome
MicroRNAs
Insulin Resistance
Adipose Tissue
Insulin
Glucose
Facilitative Glucose Transport Proteins
3' Untranslated Regions
Adipocytes
Cardiac Myocytes
Ovary
Homeostasis
Down-Regulation
Gene Expression

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chen, Y. H., Heneidi, S., Lee, J. M., Layman, L. C., Stepp, D. W., Gamboa, G. M., ... Azziz, R. (2013). miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. Diabetes, 62(7), 2278-2286.

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.

In: Diabetes, Vol. 62, No. 7, 01.07.2013, p. 2278-2286.

Research output: Contribution to journalArticle

Chen, YH, Heneidi, S, Lee, JM, Layman, LC, Stepp, DW, Gamboa, GM, Chen, BS, Chazenbalk, G & Azziz, R 2013, 'miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance.', Diabetes, vol. 62, no. 7, pp. 2278-2286.
Chen YH, Heneidi S, Lee JM, Layman LC, Stepp DW, Gamboa GM et al. miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. Diabetes. 2013 Jul 1;62(7):2278-2286.
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. In: Diabetes. 2013 ; Vol. 62, No. 7. pp. 2278-2286.
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AU - Stepp, David W.

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