ESPE Abstracts (2014) 82 NP1.2

The Role of MicroRNAs in Diabetes

Romano Regazzi

University of Lausanne, Lausanne, Switzerland

Background: MicroRNAs are small non-coding RNAs that regulate gene expression and play major roles in many physiological and pathological processes.

Objective and hypotheses: Determine whether changes in microRNA expression contribute to β-cell dysfunction and/or loss and favor the development of diabetes.

Method: Analysis of the changes in microRNA expression occurring in pancreatic islets of diabetes animal models and assessment of their functional impact in β-cells.

Results: The manifestation of diabetes is associated with alterations in the level of several microRNAs. Detailed analysis of the role of differentially expressed microRNAs revealed that some of them promote glucose-induced insulin secretion, enhance β-cell proliferation and/or improve β-cell survival, suggesting that they contribute to adaptive changes in the functional β-cell mass in response to insulin resistance. In contrast, the alterations in the level of other microRNAs result in β-cell dysfunction and death, favoring the development of diabetes. Besides their well-established regulatory function exerted inside the cells, microRNAs can be released in the extracellular space and are detected in a variety of body fluids. We provide evidence that circulating microRNAs released by activated lymphocytes can be delivered to β-cells and can affect their survival, potentially contributing to β-cell loss during the initial phases of type 1 diabetes.

Conclusion: The balance between changes in the level of microRNAs with opposing functional effects may determine whether individuals maintain blood glucose homeostasis or progress toward glucose intolerance and diabetes. We discovered that microRNAs produced by lymphocytes can be taken up by β-cells and can influence their activity, potentially contributing to the development of diabetes. Measurement of circulating microRNAs in blood or urine may provide a new class of biomarkers to predict the appearance of diabetes and its long-term complications.

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