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A team of researchers from Cornell University, the University of Cambridge, and the National Human Genome Research Institute of the National Institutes of Health has made significant advancements in understanding the role of microRNAs (miRNAs) in type 2 diabetes (T2D). The findings, published in Proceedings of the National Academy of Sciences, represent the largest study to date of diabetes-linked miRNAs found in human pancreatic islets.

The researchers analyzed nearly 65 human pancreatic islet samples from cadavers, the largest sequencing-based analysis of miRNA expression in human islets to date. The authors noted that, “Genetic studies have identified ≥240 loci associated with the risk of T2D, yet most of these loci lie in noncoding regions, masking the underlying molecular mechanisms.” They went on to say that “Recent studies investigating mRNA expression in human pancreatic islets have yielded important insights into the molecular drivers of normal islet function and T2D pathophysiology. However, similar studies investigating miRNA expression remain limited.”

The relatively large sample size allowed the researchers to determine the extent of variation in the quantity of miRNAs in the islets, or expression level, across the human population. The team also had genetic information on all the patients, which helped them determine a handful of genomic loci underlying variability in miRNA expression. One of these loci was found in the same area of the genome that is associated with T2D-related traits, suggesting a novel mechanism for how T2D develops.

Some of the most altered miRNAs in islets from individuals with T2D were consistent with those found in previous rodent studies, but there were also some notable differences. 

The researchers hope that their findings will contribute to the development of better therapeutics for T2D by improving our understanding of the molecular environment of the pancreas and what goes wrong in diabetes patients. In order to continue advancing this field, the researchers will need to invest in the development and study of human models of T2D, such as genetically-modified islets or organoids.

For more info: www.pnas.org