The researchers applied this technology to several transcription factors that reside in the pancreas and liver and were known to be associated with type 2 diabetes, but just how they contributed to the disease was unknown. They discovered that one of the transcription factors, called HNF4, controls about half of all the genes needed to make the pancreas and liver. This suggests that without HNF4, these organs could not function normally, which is particularly relevant to diabetes because the pancreas produces insulin and loss of insulin production causes the disease.
HNF4 seems to contain many of the mutations that predispose a person to type 2 diabetes, the scientists say. "This new evidence explains why defects in the HNF4 transcription factor can lead to diabetes," says Young. "Even a small loss of HNF4 function could affect the health of the pancreas because this regulator is associated with so many important genes in this organ."
Now that we understand HNF4's role, Young suggests researchers might be able to develop medications that modify the activities of mutated forms of HNF4, which could possibly prevent diabetes in some at-risk individuals. Also, these findings could enable scientists to create methods for analyzing an individual's genetic profile to determine exactly that person's risk level.
"This really changes your whole perspective," says Graeme Bell, professor of biochemistry and molecular biology at University of Chicago and co-author on the paper. "Before we were just looking at these conditions one gene at a time. Now we can see the whole playing field, and more importantly, we can see the players."