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 M Gamboa, Bo-Shiun Chen, Gregorio Chazenbalk, Ricardo Azziz

Research output: Contribution to journalArticle

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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 39UTR, 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
DOIs
StatePublished - Jan 1 2013

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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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 M; Chen, Bo-Shiun; Chazenbalk, Gregorio; Azziz, Ricardo.

In: Diabetes, Vol. 62, No. 7, 01.01.2013, p. 2278-2286.

Research output: Contribution to journalArticle

Chen, Yen Hao ; Heneidi, Saleh ; Lee, Jung Min ; Layman, Lawrence C ; Stepp, David W ; Gamboa, Gloria M ; 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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