Are extracellular microRNAs involved in type 2 diabetes and related pathologies?

MicroRNAs (miRNAs) are a class of evolutionary conserved non-coding RNAs of 19-22 nucleotides that function as negative regulators of gene expression. Originally discovered in C. elegans, miRNAs regulate fundamental cellular processes in diverse organisms, including the control of metabolic pathways involved in fat metabolism, adipocyte differentiation, energy homeostasis, glucose-stimulated insulin secretion and inflammation. Several miRNAs have been identified as having a physiological role in tissues in which type 2 diabetes (T2DM) complications occur (liver, pancreas, adipose tissue and skeletal muscle). In addition, previous studies in animal models or in human tissues have demonstrated altered expression of microRNAs in insulin-sensitive tissues of T2DM patients suggesting a potential role for these small RNA molecules in the complications associated with the diabetic condition. However all these data assume that miRNAs reside and elicit their regulatory action within the producing cells. However, studies in the last 5years have demonstrated that miRNAs are not only found intracellularly, but are also detectable outside cells, including in various body fluids. This phenomenon raises questions about the biological functions of such extracellular miRNAs. The aim of the present review is to summarize the current knowledge of the impact of extracellular miRNAs on the development of obesity-associated T2DM, and its related complications including endothelial and vascular smooth muscle cell dysfunction. It also considers the possible use of blood miRNAs as biomarkers for the detection of T2DM, classification of the disease and detection of associated pathologies.