 This new finding comes from a research article published by the Achilles Lab at Columbia University in Cell Journal in September 2012. It is titled pancreatic beta cell de-differentiation as a mechanism of diabetic beta cell failure. These scientists studied type 2 diabetes or insulin resistant diabetes. Type 2 diabetes makes up about 90% of all cases of diabetes. One of the main causes of type 2 diabetes is obesity. Because rates of obesity in type 2 diabetes have increased substantially over the past 50 years, it is important to understand the underlying biology at the level of the cell in order to engineer the next generation of therapeutics. In order to understand type 2 diabetes, let's focus on the pancreas. The important molecule we are going to talk about is insulin. When glucose in the form of sugar or starch is consumed by an individual, insulin is produced by the pancreas, by cells called beta cells. Insulin causes the cells to take up and store glucose to reduce glucose levels in the blood. So what happens in type 2 diabetic patients? Well, these patients experience something called insulin resistance. This happens when the body cannot properly use the insulin to store away glucose. As a result, glucose accumulates and the beta cells in the pancreas keep secreting more and more insulin to try and lower the blood glucose level. This causes a lot of stress on the beta cell and eventually the patient experiences beta cell failure, where the pancreas is no longer able to produce insulin and blood glucose remains high. This paper addresses the issue of beta cell failure and tries to understand why beta cells become unable to produce insulin. To start talking about this finding, let's understand where beta cells come from. Beta cells come from stem cells that we call progenitor cells that are specialized in producing a variety of cells for the pancreas. What happens is a progenitor cell will divide and those cells it produced will undergo a process called differentiation, where they become beta cells that produce insulin or other cell types in the pancreas. What's important to know is that this is a one-way street, so beta cells cannot make stem cells. Before this finding came out, there was much controversy in the field trying to understand why beta cells can no longer produce insulin in type 2 diabetic patients. Some scientists thought that the beta cells died more quickly than they were replenished, which caused a net reduction in the number of cells that produced insulin. But what this paper is showing is something a little different. In this paper, the authors are using a mouse model of type 2 diabetes that develops beta cell failure. What the authors did is looked at what happens to the beta cells over time when a mouse experiences beta cell failure. To do this, they engineered the mouse so that all beta cells that made insulin were yellow. If a beta cell loses its ability to make insulin, it turns green. So now they are able to answer their question, what causes beta cell failure and what happens to the beta cells? If beta cells were dying more quickly than new cells were being made, as was previously thought, then the number of yellow cells would go down and there would be no green cells. But that is not what they saw. In contrast, the authors saw that the number of green cells was actually going up with beta cell failure. This means that beta cells were losing their ability to make insulin. The beta cells weren't dying at all, but they were changing into cells that don't produce insulin. So what are these new green cells? Well, it turns out that these new green cells are actually progenitor cells, the same progenitor cells that normally produce beta cells. The beta cells undergoing beta cell failure have gone back in time to become the progenitor cells that produced them. This process is called de-differentiation, but it had never before shown to occur in response to beta cell failure. So this is very exciting. What's even more exciting is that these green de-differentiated cells are then able to make a variety of different cells for the pancreas. So this finding is very interesting for a number of reasons. Number one, it provides a new understanding of the causes of type 2 diabetes that was not previously known. Number two, it suggests that there is no loss of cells in type 2 diabetes. So these new progenitor cells may still have the ability to turn back into beta cells and reverse beta cell failure to maybe cure type 2 diabetes. So what did this study show? This study showed that during beta cell failure, which causes type 2 diabetes, beta cells that normally make insulin de-differentiate to become the progenitor cells that created them. These new progenitor cells now have the ability to produce other cells for the pancreas. This finding is very exciting, but when thinking about therapies for type 2 diabetes, it is still very preliminary. The authors use a mouse model for type 2 diabetes, so it's not clear if this is also what happens in humans during type 2 diabetes development or even in a different mouse model of type 2 diabetes. As you can see, scientists are always trying to rethink the status quo to gain knowledge and learn the truth about the causes of diseases to develop more efficient and targeted therapies.