New research in mice suggests a novel way to treat both forms of diabetes. 1130945222 Tom Werner/Getty Images
- Scientists have used synthetic antibodies to block cell receptors in the liver that normally bind to glucagon, a hormone involved in increasing the amount of glucose in the blood.
- The antibodies restored normal blood glucose levels in three different mouse models of diabetes.
- The treatment partly worked by transforming alpha cells in the pancreas into insulin-producing beta cells.
- The researchers believe that the same approach could treat type 1 and type 2 diabetes in people.
Diabetes keeps the body from being able to regulate levels of glucose in the blood. In the long term, this can lead to a wide range of life-changing complications, including vision loss, kidney damage, stroke, and heart disease.
In the United States, estimates suggest that around 34.2 million people have either diagnosed or undiagnosed diabetes. Type 2 diabetes accounts for 90–95% of these cases.
In healthy individuals, the concentration of glucose in the blood is maintained at optimum levels through the opposing effects of two hormones, insulin and glucagon.
Beta cells in the pancreas produce insulin, which stimulates cells around the body to extract glucose from the bloodstream.
Other cells in the pancreas, called alpha cells, produce glucagon, which increases the amount of glucose that the liver releases into the bloodstream.
In type 1 diabetes, the immune system targets beta cells, reducing insulin production.
By contrast, in type 2 diabetes, cells around the body become resistant to the effects of insulin. Beta cells respond by producing more and more of the hormone and eventually die.
Blocking glucagon receptors
Previous research in mice suggested that a synthetic, or “monoclonal,” antibody that blocks glucagon receptors in the membranes of liver cells could restore normal blood glucose levels. However, it wasn’t entirely clear how this worked.
Now, a team led by researchers at the University of Texas Southwestern Medical Center, in Dallas, has discovered that blocking glucagon receptors has the indirect effect of transforming alpha cells in the pancreas into beta cells.
The newly created beta cells produce insulin, which helps lower levels of glucose circulating in the blood.
Currently, some people with diabetes use insulin injectors or pumps to regulate their glucose levels, but these treatments are not perfect.
Though people with 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,” explains study leader Dr. May-Yun Wang, an assistant professor of internal medicine at the medical center.
“Giving them back their own beta cells could help restore much better natural regulation, greatly improving glucose regulation and quality of life,” she continues.
Transforming alpha cells into beta cells could be a particularly promising treatment for type 1 diabetes, says Dr. William L. Holland, the senior study author, who is now an assistant professor of nutrition and integrative physiology at the University of Utah, in Salt Lake City.
“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,” he explains.
“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.”
The research has been published in the Proceedings of the National Academy of Sciences.
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