Emerging roles of non-coding RNAs in pancreatic ß-cell function and dysfunction.

Pancreatic ß-cells play a central role in glucose homeostasis by tightly regulating insulin release according to the organism's demand. Impairment of ß-cell function due to hostile environment, such as hyperglycaemia and hyperlipidaemia, or due to autoimmune destruction of ß-cells, results in diabetes onset. Both environmental factors and genetic predisposition are known to be involved in the development of the disease, but the exact mechanisms leading to ß-cell dysfunction and death remain to be characterized. Non-coding RNA molecules, such as microRNAs (miRNAs), have been suggested to be necessary for proper ß-cell development and function. The present review aims at summarizing the most recent findings about the role of non-coding RNAs in the control of ß-cell functions and their involvement in diabetes. We will also provide a perspective view of the future research directions in the field of non-coding RNAs. In particular, we will discuss the implications for diabetes research of the discovery of a new communication mechanism based on cell-to-cell miRNA transfer. Moreover, we will highlight the emerging interconnections between miRNAs and epigenetics and the possible role of long non-coding RNAs in the control of ß-cell activities.

Role and therapeutic potential of microRNAs in diabetes.

The discovery in mammalian cells of hundreds of small RNA molecules, called microRNAs, with the potential to modulate the expression of the majority of the protein-coding genes has revolutionized many areas of biomedical research, including the diabetes field. MicroRNAs function as translational repressors and are emerging as key regulators of most, if not all, physiological processes. Moreover, alterations in the level or function of microRNAs are associated with an increasing number of diseases. Here, we describe the mechanisms governing the biogenesis and activities of microRNAs. We present evidence for the involvement of microRNAs in diabetes mellitus, by outlining the contribution of these small RNA molecules in the control of pancreatic beta-cell functions and by reviewing recent studies reporting changes in microRNA expression in tissues isolated from diabetes animal models. MicroRNAs hold great potential as therapeutic targets. We describe the strategies developed for the delivery of molecules mimicking or blocking the function of these tiny regulators of gene expression in living animals. In addition, because changes in serum microRNA profiles have been shown to occur in association with different human diseases, we also discuss the potential use of microRNAs as blood biomarkers for prevention and management of diabetes.