In a new large-scale genetic analysis, scientists have found a set of small RNA molecules, called microRNAs (miRNAs), in human pancreatic cells that are strongly associated with type 2 diabetes. Researchers discovered the miRNAs in groups of cells called pancreatic islets, which produce hormones, such as insulin, that the body uses to regulate energy levels.
The study, led in part by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, will inform future studies on the early detection and treatment of diabetes. The results were published in Proceedings of the National Academy of the Sciences.
Role of miRNAs in the etiology of diabetes
In people with diabetes, the islets fail to produce sufficient insulin to control blood sugar, which is why understanding the basic biology of pancreatic islets is important for human health.
Previous research with animal or cell-based models over the past two decades suggests that certain miRNAs, that are involved in controlling which genes are turned on and off in cells, may help pancreatic islets normally develop and function. However, the specific role of these miRNAs in human pancreatic islets was poorly characterized.
“This study represents the largest sequence-based analysis of miRNA expression in human pancreatic islets to date,” said Francis Collins, MD, PhD, senior investigator in the Center for Precision Health Research in NHGRI’s Intramural Research Program and senior author of the study. “The results of this study set the stage for understanding how miRNAs fine-tune gene expression in pancreatic islets and its implications for diabetes.”
Using next-generation DNA sequencing, a fast and high-throughput method for sequencing nucleic acids, the researchers analyzed miRNAs in over 60 samples of human pancreatic islets. They found specific miRNAs that are different in people with type 2 diabetes, which may be important for charting the course of the condition or for the future development of drug therapies.
“Some of the human pancreatic islet miRNAs we found to be associated with diabetes have not been well-studied previously,” said Praveen Sethupathy, PhD, professor of physiological genomics at Cornell University, Ithaca, New York, and senior author of the study. “The majority of prior studies have been in rodents or in islet-like groups of cells growing in a dish. It has not been clear whether or to what extent the discoveries made in these studies are relevant to human pancreatic islets and diabetes.”
The researchers also found genomic variants that are associated with the quantity (or expression level) of certain miRNAs in the cell. These genomic variants might explain the variation seen in the level of specific miRNAs among different people. One of these genomic variants was found in a genomic region known to be associated with increased risk for type 2 diabetes-related traits, which may give researchers clues about how type 2 diabetes develops.
Why is this study important?
Diabetes affects more than 37 million Americans—about one in 10 people. Approximately 90–95 percent of people with diabetes have type 2 diabetes, in which the body either does not make enough insulin and/or is unable to use insulin properly. The hallmark feature of diabetes is too much sugar circulating in the bloodstream. Prolonged high blood sugar levels can lead to heart disease, kidney disease, and vision loss. Currently, diabetes has no cure, but treatment and lifestyle changes can help individuals manage the condition.
“Based on this work, and building on previous studies, we hope one day to be able to identify accurate miRNA biomarkers for early detection and treatment of diabetes and improve outcomes for patients in the future,” said Henry Taylor, PhD, candidate at the University of Cambridge, an NIH Oxford-Cambridge Scholar, and first author of the study.
- This press release was originally published on the National Human Genome Research Institute website