Diabetes research news (and anything involving lab mice) can sometimes make our eyes gloss over, as it seems we’re hearing about some new scientific “breakthrough” every other day.
But we took a little more interest recently when hearing about a new line of D-research that seems to have a Star Trek spin to it!
Yup, apparently this research is exploring how our insulin-producing cells basically put on a Romulan cloaking device to hide from diabetes!
Specifically, a certain Dr. Domenico Accili, director of the Columbia University Diabetes and Endocrinology Research Center, and his team appear to have discovered that in type 2 diabetes at least, the beta cells don’t die off completely; rather, they go into hiding.
Take a read of this Discover article on Dr. Accili’s research titled “Why Type 2 Diabetes is a Bit Like the Bourne Identity,” which explains:
“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 specialized identities and become more of a tabula rasa. In the film, it’s simple memory loss. In the cells, it’s known as ‘dedifferentiation.‘”
It all goes back to the medical mystery of what causes diabetes (both types!). The current explanation for type 2 diabetes is that obesity plus a host of other factors (including race, genetics, etc.) cause insulin resistance.
Even if the diabetes is managed well, the insulin resistance often increases over time to the point where the type 2 PWD is required to start taking insulin. Common theory is that the beta cells have been worked to death at that point, but a recent New York Times article quoted Alan Saltiel, director of the Life Sciences Institute at the University of Michigan, that in reality: “we have no idea what’s going on.”
Dr. Accili’s team of researchers observed that beta cells in genetically-modified mice don’t actually die off. Instead, they revert back into their “progenitor” state, which is one of several steps that a cell goes through on its way to becoming a full-grown, specialized cell. All cells start off as embryonic stem cells, which then turn into progenitor cells. Progenitor cells can still specialize into a few different types of cells, but they aren’t quite as footloose and fancy free as embryonic stem cells. Once a cell becomes differentiated into a new form, it’s stuck for life, i.e. once a beta cell, always a beta cell.
In their research, Dr. Accili and his team noticed something about a specific protein, called dFoxO. When a beta cell is healthy, the dFoxO protein doesn’t do much. It just floats around in the cell. But when a beta cell is stressed from hypoglycemia, the proteins are activated and start moving around the cell.
“As hyperglycemia continues, gradually these proteins disappear from the beta cell,” Dr. Accili explains.
But the dFoxO proteins don’t just spontaneously combust. They actually head inside the cell’s nucleus, which you might remember from Freshman Biology is the “cell’s brain.” Once the protein is inside the nucleus, the protein causes the cell to revert back to the progenitor cell.
“The existence of the protein keeps the beta cell from being a progenitor cell,” Dr. Accili says. “Diabetes kills the protein, so the cells turn back.”
As noted, the main implication is that beta cells in type 2 diabetes might not be dead after all, which means they could be revived and start producing insulin again (!) Dr. Accili says this discover might have a positive implications for type 1 diabetes, too. How? you might wonder. After all, type 1 diabetes is an autoimmune disease and type 2 diabetes is metabolic…
“We’ve known that even in type 1, some cells don’t die,” Dr. Accili explains. “We’ve been wondering, ‘How are these cells not dead?’ We think that the reason they might not be dead is that they’re also hiding as progenitor cells. They are resistant to the immune attack while in hiding, so the immune system doesn’t attack.”
“Kind of like a Romulan cloaking device on Star Trek?” I asked during our interview (admitting my no-so-cloaked geekiness).
Dr. Accili laughed. “Yes, exactly.”
To be clear, the disappearing dFoxO proteins don’t cause either type of diabetes. The loss of this protein is more of an aftershock that then causes the progressive nature of type 2 diabetes. After long enough exposure to hyperglycemia, the beta cells do get stressed out. This is a natural part of the disease process, and not something a little bit of yoga can change.
But if Dr. Accili’s team could harness these hidden cells for dedifferentiation, “Type 2 diabetes could be frozen in its tracks and possibly reversed,” he says.
Remember, so far this research is in mice only; they are currently working with both for-profit and non-profit organizations to conduct research on cadaveric pancreases to see if dFoxO proteins also disappear in humans. If that’s the case, then researchers will work on developing a treatment to coax the dFoxO proteins out so that beta cells feel safe to come out of hiding.
For type 2 diabetes, the responsibility of a “cure” has typically rested squarely on the patient’s shoulders. But now it looks like there are more chances than ever to possibly regenerate beta cells.
We’ll keep you posted on Dr. Accili and his Star Trek enterprise!