Deconstructing Diabetes

More than 15 million people in the United States have type 2 diabetes, but its causes are varied and not well understood. Researchers at the Whitehead Institute for Biomedical Research, MIT, and the University of Chicago have used new genomic-analysis methods to unravel some of the disease's mysteries.

Previously, scientists had found signs that certain biological molecules were linked to type 2 diabetes. The suspect molecules were transcription factors, a type of molecule that binds to specific parts of the genome to switch genes on at the right time to create the myriad tissues that make up all the body's organs. Until recently, figuring out which genes a transcription factor regulates was a prohibitively time-consuming process. However, the researchers have developed a technique for performing such analyses hundreds to thousands of times faster.

The technique allowed the researchers to determine whether various transcription factors found in the liver and the pancreas interact with any of 13,000 human genes. They found that a single transcription factor, HNF4, was involved in the expression of about half of the genes containing the instructions to create pancreas and liver cells, whereas other factors interacted with only a small percentage of those genes. Because HNF4 proved to be so active in the formation of liver and pancreatic cells, the researchers can now explain how a defective version of it could contribute to diabetes.

"This one transcription factor seems to be the key," says Duncan Odom, a Whitehead postdoctoral fellow and lead author of the recent paper in the journal Science that described the researchers' findings. Their results could one day be used to identify people at risk for developing diabetes as adults. In the meantime, Odom is working to uncover the roles of several other transcription factors in the liver and pancreas.