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Int J Mol Sci. 2018 Nov 22;19(12). pii: E3705. doi: 10.3390/ijms19123705.

MicroRNAs as Regulators of Insulin Signaling: Research Updates and Potential Therapeutic Perspectives in Type 2 Diabetes.

Author information

1
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. launigi@gmail.com.
2
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. giusy.grieco.90@gmail.com.
3
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. giulianaventriglia@gmail.com.
4
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. noemibrusco91@gmail.com.
5
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. francescamancarella90@gmail.com.
6
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. catefo@libero.it.
7
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. francesco.dotta@alice.it.
8
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy. sebastianiguido@gmail.com.

Abstract

The insulin signaling pathway is composed of a large number of molecules that positively or negatively modulate insulin specific signal transduction following its binding to the cognate receptor. Given the importance of the final effects of insulin signal transduction, it is conceivable that many regulators are needed in order to tightly control the metabolic or proliferative functional outputs. MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively modulate gene expression through their specific binding within the 3'UTR sequence of messenger RNA (mRNA), thus causing mRNA decoy or translational inhibition. In the last decade, miRNAs have been addressed as pivotal cellular rheostats which control many fundamental signaling pathways, including insulin signal transduction. Several studies demonstrated that multiple alterations of miRNAs expression or function are relevant for the development of insulin resistance in type 2 diabetes (T2D); such alterations have been highlighted in multiple insulin target organs including liver, muscles, and adipose tissue. Indirectly, miRNAs have been identified as modulators of inflammation-derived insulin resistance, by controlling/tuning the activity of innate immune cells in insulin target tissues. Here, we review main findings on miRNA functions as modulators of insulin signaling in physiologic- or in T2D insulin resistance- status. Additionally, we report the latest hypotheses of prospective therapies involving miRNAs as potential targets for future drugs in T2D.

KEYWORDS:

diabetes mellitus; insulin; insulin signaling; microRNAs

PMID:
30469501
PMCID:
PMC6321520
DOI:
10.3390/ijms19123705
[Indexed for MEDLINE]
Free PMC Article

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