Why type 2 diabetes is a bit like The Bourne Identity

By Ed Yong | September 14, 2012 11:21 am

In The Bourne Identity, the eponymous hero is presumed dead by his former employers, but turns out to have merely lost his memory. Thus unburdened, he attempts to change his fate.

Which reminds me of diabetes.

People with type 2 diabetes face two problems, both related to insulin – the hormone that regulates the levels of sugar in our blood. They don’t respond properly to it (they become insulin resistant), and they don’t make enough of it. As a result, the levels of sugar in their blood become too high. Insulin resistance is fairly steady throughout a person’s lifetime, but the failure to make insulin gets progressively worse. The typical explanation is that the beta-cells – a type of insulin-making cells within the pancreas – die off.

But Domenico Accili from Columbia University has a different idea. By studying diabetic mice, he has found beta-cells do indeed disappear over time, but not because they die. Instead, they revert back to a more basic type of cell that doesn’t produce insulin. Like Jason Bourne, they lose their former specialised identities and become more of a tabula rasa. In the film, it’s simple memory loss. In the cells, it’s known as “dedifferentiation”.

And like Jason Bourne, these pre-beta cells can take on new fates—they can turn into other pancreatic cells, which make other hormones. These include glucagon, which acts as insulin’s antagonist, opposing its effects on blood sugar levels. This explains why a diabetic pancreas not only loses the ability to make insulin, but starts making more glucagon instead.

Accili’s team member Chutima Talchai found that the beta-cells depend on a protein called FoxO1 to stop themselves from dedifferentiating. Without this handler, they spontaneously reverted to the pre-beta state whenever the mice experienced bouts of physical stress, such as pregnancy or even ageing.

In humans, Accili thinks that a continuous storm of fats and carbohydrates could have the same effect. His working hypothesis is that a bad diet stresses the beta-cells, forcing them to produce insulin beyond their normal capacity. Rather than work themselves to death, the cells enact a self-preservation programme that turns them back into a simpler state that isn’t responsible for making insulin. (At this point, it becomes impossible to stretch the Bourne metaphor without spoilers. Go see the film. There’s a nice bit with a magazine.)

It’s an intriguing idea, and one that he will try to confirm in a later study. Also to be confirmed: whether this applies to humans as well as mice. Peter Butler, a diabetes specialist at the University of California, Los Angeles, praised Accili’s study but told me that many discoveries in diabetic mice have failed to translate to humans.

This is clearly the big question to answer: does the pancreas of someone with type 2 diabetes have more of these pre-beta cells than a healthy person? If so, it may be possible to devise new treatments for the condition by finding compounds that can stop the beta-cells from dedifferentiating.

NB: This post is an adaptation of a piece I wrote for The Scientist, so head over there for a more detailed version.

Reference: Talchai, Xuan, Lin, Sussel & Accili. 2012. Pancreatic beta-Cell Dedifferentiation as a Mechanism of Diabetic beta-Cell Failure. Cell http://dx.doi.org/10.1016/j.cell.2012.07.029

CATEGORIZED UNDER: Medicine & health

Comments (6)

  1. Great angle!

    I guess the race will be on to quantify human pre-beta cells and see if it does translate; then work out if there’s some way of delivering something to differentiate them. But not all of them, if they’re present in healthy individuals, presumably that could mess up some other part of metabolism. Tricksy.

    Nice bit of research though.

  2. Zach Miller

    I assume it’s different for the cause of diabetes in CF patients, though…

  3. Fun article and interesting analogy! Thanks, Ed.
    Of course, as someone preoccupied with stem cells, I immediately also think of iPS cells and cellular reprogramming. Stem cell scientists are trying to make other cells of the pancreas turn into beta cells called “transdifferentiation”. Another approach is to make iPS cells from diabetic patients’ skin and then convert the iPS cells into beta cells.
    One overall take home message is that cells are far more “plastic” than cell biologists have believed for the last several decades. Of course characters in movies are that way too, but what about people in real life? Change our diet, our niche, our job…over time will we change into different people at some level?

  4. Patricia

    If true that beta cells change in order to protect themselves from overwork, then what would happen if a treatment kept them from changing? Would they then self-destruct? Also, the drugs that stimulate the beta cells to produce more insulin may just be hastening their destruction (or change).

    It is quite possible that the hypoglycemic drugs do nothing more than change the surrogate markers of diabetes, blood glucose numbers. Doctors and patients are beling lulled into a false sense of security by seeing the numbers go down, when in fact, the underlying disease may still be taking its toll on the body. The next few decades will tell as patients age and the drugs get the real test they need to see if they produce meaningful results in terms of a reduction in complications from the disease. It could be that the only meaningful treatment for type 2 diabetes remains diet and exercise (especially exercise!), and even then, age may eventually win out in the progression of the disease.

  5. Bob

    This is a promising lead. Yet another link between bad diet and diabetes, and one that makes sense as well. Hopefully it will lead to a finding in humans and better treatment.

    Also, I don’t think you need to worry about spoiling The Bourne Identity. Anyone who wanted to see it has seen it already.

  6. So if I eat enough junk food, will my pancreatic cells…

    *Spoiler Alert*

    …hook up with a beautiful French girl?


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