NEW YORK – JDRF-funded researchers have identified a key signal that prompts existing insulin-producing beta cells in the pancreas to form new beta cells in mice, a breakthrough discovery that may ultimately help researchers find ways to restore or increase beta cell function in people with type 1 diabetes.
The study, led by Yuval Dor, Ph.D., a professor at the Institute for Medical Research Israel-Canada, the Hebrew University of Jerusalem, shows for the first time that a high rate of glucose metabolism, a process that converts glucose into energy that cells can use, triggers beta cells to regenerate. Coupled with a mechanism that prevents the immune system from attacking beta cells in the first place, the long-awaited finding may help pave the way to a full cure for type 1 diabetes. The study, which took five years to complete, will be published in the April 6 issue of Cell Metabolism.
“Our work shows that as glucose is metabolized, it tells the beta cells to regenerate,” says Dor, who is also a 2010 recipient of the JDRF Gerold and Kayla Grodsky Basic Research Scientist Award. “It’s not blood glucose per se that is the signal, but the glucose-sensing capacity of the beta cell that’s key for regeneration.”
In type 1 diabetes, the immune system launches a misguided attack on insulin-producing beta cells, resulting in their eventual loss and decline of function. Without insulin, the body’s cells cannot absorb glucose from the blood and use it for energy. As a result, glucose accumulates in the blood, leaving the body’s cells and tissues starved for energy. That’s why people with the disease must inject insulin and monitor their blood glucose levels vigilantly every day, multiple times a day, to stay alive and maintain optimal health.
In their work, Dor and co-lead author Benjamin Glaser, M.D. of Hadassah Medical Center, used a genetic system to destroy 80 percent of the insulin-producing cells in adult mice, rendering the mice diabetic. When the researchers compared these mice with control mice, they found that those mice with diabetes and elevated blood glucose levels had regenerated a greater number of new beta cells than mice without diabetes, suggesting that glucose is a key player in beta cell regeneration.
To determine how glucose plays a role in triggering beta cells to regenerate or proliferate, the researchers tweaked various steps in the glucose metabolism pathway within the beta cell. They found that an enzyme, glucokinase, which triggers the first step in converting glucose for energy, also stimulates beta cells to replicate.
“This means that the more work that beta cells are required to do, the more of themselves they make,” says graduate student Shay Porat, who, along with Noa Weinberg, spearheaded the study.
Because this study also showed that regeneration depends on glucokinase levels, rather than glucose levels, researchers may be able to use drugs to trigger beta cells to regenerate without exposing the body to elevated glucose levels, which can cause organ damage and even kill beta cells. The finding may pave the way for developing a new kind of drug or therapy to modulate glucokinase or other steps in the glucose-sensing pathway to direct beta cells down the path of regeneration and survival rather than death.
“This study shows that pharmacologic activators of glucokinase, a novel class of drugs being developed for the treatment of type 2 diabetes because of their ability to increase insulin production, also have the ability to increase beta cell replication,” says Patricia Kilian, Ph.D., director for regeneration research at JDRF. “These or other drugs which affect glucose metabolism in the beta cell may have additional benefits for helping to restore beta cell function in both type 1 and type 2 diabetes. That’s our hope.”
Regeneration Research at JDRF
Among the fastest-growing scientific areas that JDRF supports is research aimed at protecting and regenerating insulin-producing cells in people who are at risk or have diabetes. This includes finding therapies to trigger the body to increase the number of beta cells, either by forming new beta cells from existing ones – some beta cells may be present even in people who have had diabetes for decades – or inducing the formation of new beta cells from a precursor or other cell types in the pancreas.
JDRF has been a leader in this new and exciting research field. The foundation funds a wide range of research projects that include pinpointing the signals that prompt beta cells to regenerate, such as the Dor study, as well as creating innovative diabetes drug discovery and development partnerships focused on beta cell regeneration.
JDRF is the worldwide leader for research to cure type 1 diabetes. It sets the global agenda for diabetes research, and is the largest charitable funder and advocate of diabetes science worldwide.
The mission of JDRF is to find a cure for diabetes and its complications through the support of research. Type 1 diabetes is an autoimmune disease that strikes children and adults suddenly, and can be fatal. Until a cure is found, people with type 1 diabetes have to test their blood sugar and give themselves insulin injections multiple times or use a pump – each day, every day of their lives. And even with that intensive care, insulin is not a cure for diabetes, nor does it pre-vent its potential complications, which may include kidney failure, blindness, heart disease, stroke, and amputation.
Since its founding in 1970 by parents of children with type 1 diabetes, JDRF has awarded more than $1.5 billion to diabetes research, including $107 million last year. More than 80 percent of JDRF’s expenditures directly support research and research-related education. For more information, please visit www.jdrf.org.
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