Researchers See Promise In Diabetes Treatment By Transforming Alpha Cells Into Beta Cells

Clinical Advisor

According to the Centers for Disease Control and Prevention (CDC), diabetes is described as ‘a chronic (long-lasting) health condition that affects how your body turns food into energy.’

Your body works to break down the food you eat into sugar, which is also known as glucose, which is released into your bloodstream. When the blood sugar starts to go up, it’s a signal to your pancreas to discharge insulin. The insulin works as a sign to allow the blood sugar into your body’s cells in order to use it as energy.

When someone suffers from diabetes, it means that their bodies either don’t make enough insulin, or their bodies can’t use the insulin they do make the way they should. Regardless of which type of diabetes one has, it leads to too much blood sugar getting stuck in their bloodstream, eventually leading to an array of serious health problems like heart disease, vision loss, stroke and kidney damage.

According to the CDC, at least 34.2 million Americans suffer from diabetes, which is basically just over 1 in 10, with another 88 million having prediabetes. And around 90 to 95% of the 30 plus million have Type 2 diabetes. And while there is no cure for this disease, there are a number of treatments patients can use, depending on what their doctor prescribes to them.

In an attempt to find better treatments, scientists have worked with ‘synthetic antibodies to block cell receptors in the liver that normally bind to glucagon,’ which is a hormone that’s used by the body to increase the amount of glucose released in the blood.

What these antibodies have managed to do is restore normal blood glucose levels in at least three different mouse models of diabetes. The treatment managed to partly work by converting alpha cells in the pancreas into insulin-generating beta cells.

The researchers also thought that they could use the same approach to treat both type 1 and type 2 diabetes in humans.

For individuals that are considered healthy, most of the glucose in their blood is normally maintained ‘at optimum levels through the opposing effects of two hormones, insulin and glucagon.

Beta cells, on the other hand, which can be found in the pancreas produce insulin, and this is what stimulates the cells around the body to extract glucose from the bloodstream. Meanwhile, the other cells in the pancreas, which are known as alpha cells, produce glucagon, ‘which increases the amount of glucose that the liver releases into the bloodstream.’

For patients that have type 1 diabetes, their immune system targets the beta cells, therefore reducing the insulin production. However, in type 2 diabetes, the cells around the body become resistant to the effects of the insulin their bodies produce. Such beta cells behave by creating more and more of the hormone until they eventually die.


How Blocking Glucagon Receptors Works

In former research done in mice, it showed that a synthetic or “monoclonal” antibody that usually blocks the glucagon receptors in the liver cell membranes could work to restore normal blood glucose levels. But, it wasn’t exactly clear as to how this actually worked.

But now, a research team from the University of Texas Southwestern Medical Center in Dallas has since discovered ‘that blocking glucagon receptors has the indirect effect of transforming alpha cells in the pancreas into beta cells.’ And since the newly produced beta cells produce insulin, they then help lower the levels of the glucose that’s circulating within the blood.

One type of treatment for some patients with diabetes is using insulin injectors or pumps to help them regulate their glucose levels. But the problem with this is that they aren’t perfect treatments.

According to study leader and assistant professor of internal medicine at the medical center, Dr. May-Yun Wang, while those with either type 1 or type 2 diabetes “try their very best to keep glucose under control, it fluctuates quite massively throughout the day, even with the best state-of-the-art pump.”

“Giving them back their own beta cells could help restore much better natural regulation, greatly improving glucose regulation and quality of life,” she adds.

Another senior study author and assistant professor of nutrition and integrative physiology at the University of Utah in Salt Lake City, Dr. William L. Holland, shares that transforming alpha cells into beta cells could be a truly promising treatment for type 1 diabetes.

He explains, “Even after decades of an autoimmune attack on their beta cells, type 1 diabetics will still have plentiful amounts of alpha cells. They aren’t the cells in the pancreas that die.”

“If we can harness those alpha cells and convert them into beta cells, it could be a viable treatment for anyone with type 1 diabetes,” he adds.

To learn more about their research, you can check out the published study in the Proceedings of the National Academy of Sciences.


The Three Mouse Models of Diabetes

In order to figure out and understand what happens when the antibodies block the glucagon receptors, the research team came up with experiments in three different mouse models of diabetes.

For the first model, it was a genetic mutation induced apoptosis – otherwise known as “cell suicide” – in the beta cells response to a particular chemical treatment.

In patients that suffer from type 1 or type 2 diabetes, the loss of the beta cells lessened the animals’ abilities to create insulin, which then make it harder to regulate their glucose levels. Researchers noted that when they gave the mice weekly injections of the glucagon receptor antibodies, the treatment managed to substantially lower the animal’s blood glucose levels.

Incredibly, the improvement lasted for weeks, even after the injections had stopped. For those mice in this study using these treatments, the antibodies managed to indirectly boost the number of beta cells within the pancreas by almost sevenfold.

In order to figure out where the excess beta cells were coming from, the study group used a technique called lineage tracing so they could label the alpha cells in the pancreas, then track them as they went through a number of rounds of division. They also found out that the treatment managed to convert some of the cells into beta cells that produced insulin.


When Under Immune Attack

The research group wasn’t sure if the treatment would work when the immune system attacked the beta cells, which is what happens when patients have type 1 diabetes.

In order for researchers to mimic the effect, they used another model with non-obese yet diabetic mice where the animal’s immune system drained their beta cells. The research team treated the mice using monoclonal antibodies, which despite the continuous immune attacks, the animals’ beta cell numbers still rebounded.

Lastly, the researchers decided to test if the treatment would work in human pancreas cells. In order to do this, the team grafted pancreatic tissue with alfa and beta cells into non-obese diabetic mice, but still in numbers small enough to make sure that the animals were still mildly diabetic.

The team then treated the mice with antibodies against the glucagon receptor, the human beta cells proliferated, which helped restore the blood glucose regulation in the mice.

The researchers shared in their paper, “These studies provide hope that a once-weekly injection of a human antibody against the glucagon receptor can enhance functional [beta cell numbers].” Researchers also hope that “Changing small amounts of residual [beta] cells can have a huge improvement in the quality of life for millions of patients with type 1 diabetes.”

They note that one particular limitation of their research was due to the difficulty of accurately determining if the amount of human beta cells changed as a response to their treatment.

Yet, they also conclude, “These studies provide hope that a once-weekly injection of a human antibody against the glucagon receptor can enhance functional [beta cell] mass.”