This new finding comes from a research article published by the Accili lab at Columbia University
in Cell journal in September 2012.
It is titled “Pancreatic B cell dedifferentiation as a mechanism of diabetic B 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 and 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
in the pancreas by cells called B 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 B 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 cells 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 this issue of “beta cell failure” and tries to understand WHY
beta cells become unable to make insulin.
To start talking about this finding, lets 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 will undergo a process called
“differentiation” where they become beta cells that produce insulin.
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.
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 produce insulin.
What this paper is showing is something a little different.
The authors are using a mouse model of type 2 diabetes that develops beta cell failure
and type 2 diabetes.
What the authors did is they 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?
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 do not
produce insulin.
What are these new green cells?
Well it turns out that these new green cells are actually progenitor cells!
The same progenitor (or stem) 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 been shown to occur
in response to beta cell failure in the pancreas.
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.
This finding is very exciting for a number of reasons:
#1- it provides a new understanding of the causes of type 2 diabetes that was not previously
known #2- it suggests that there is no LOSS of cells
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 can then 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 used a mouse model for type 2 diabetes so its not clear if this is also
what happens in humans during type 2 diabetes 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.