miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance.
miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance.
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miRNA-93抑制GLUT4，并在多囊卵巢综合征患者和具有胰岛素抵抗的女性的脂肪组织中过表达。
作者：
Chen YH;Heneidi S;Lee JM;Layman LC;Stepp DW;Gamboa GM;Chen BS;Chazenbalk G;Azziz R
大约70%的多囊卵巢综合征（PCOS）女性具有内在的胰岛素抵抗（IR），超过与体重相关的IR，包括脂肪组织中葡萄糖代谢功能障碍（AT）。在AT中，IRS/PI 3-K/AKT通路信号成分的分析确定只有GLUT 4表达在PCOS患者和IR对照组中显著降低。我们研究了miRNA的作用，特别是在调节GLUT 4（胰岛素敏感性葡萄糖转运蛋白）中的作用。PCOS AT被确定具有差异表达的miRNA谱，包括上调的miR-93、-133和-223。GLUT 4是miR-93的高度预测靶点，而miR-133和miR-223已被证明可调节心肌细胞中的GLUT 4表达。miR-93的表达揭示了体内IR值的稳态模型评估与人AT中的GLUT 4和miR-93而不是miR-133和-223表达之间的强相关性。miR-93的过表达通过直接靶向GLUT 4 3′UTR导致脂肪细胞中GLUT 4基因表达下调，而miR-93活性的抑制导致GLUT 4表达增加。这些结果指出了一种通过miR-93调节胰岛素刺激的葡萄糖摄取的新机制，并证明了在所有PCOS和患有IR的非PCOS女性中miR-93表达上调，可能解释了该综合征的IR。相比之下，miR-133和miR-223可能在PCOS的IR中具有不同的作用，尽管尚未确定。
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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影响因子：
3.7
作者：
Chazenbalk G;Bertolotto C;Heneidi S;Jumabay M;Trivax B;Aronowitz J;Yoshimura K;Simmons CF;Dumesic DA;Azziz R
通讯作者：
Azziz R
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
8.2
作者：
Herrera, B. M.;Lockstone, H. E.;Taylor, J. M.;Ria, M.;Barrett, A.;Collins, S.;Kaisaki, P.;Argoud, K.;Fernandez, C.;Travers, M. E.;Grew, J. P.;Randall, J. C.;Gloyn, A. L.;Gauguier, D.;McCarthy, M. I.;Lindgren, C. M.
通讯作者：
Lindgren, C. M.
影响因子：
8.9
作者：
Heneghan, H. M.;Miller, N.;Kerin, M. J.
通讯作者：
Kerin, M. J.