Researchers at the Icahn School of Medicine at Mount Sinai in New York report they’ve discovered a common drug used to treat specific bone conditions can actually stimulate the production of beta cells to help control diabetes.
The drug, denosumab, is already approved by the Food and Drug Administration (FDA) for the treatment of osteoporosis and certain bone tumors. In a study using mice, researchers say the drug uses a well-known bone-related pathway to increase pancreatic beta cells.
Your pancreas is responsible for producing beta cells, which secrete insulin in response to increased blood sugar. For diabetics, the immune system incorrectly targets these cells so they aren’t able to produce insulin to control glucose.
“Our study identifies a molecular brake that inhibits both mouse and human beta cell replication,” Rupangi Vasavada, Ph.D., senior study author and associate professor of medicine, endocrinology, and diabetes at Mount Sinai, said in a press release. “It shows that two proteins, including an FDA-approved osteoporosis drug, can override and release this brake to induce proliferation of rodent and human beta cells.”
A Needed Treatment for Diabetes
According to the U.S. Centers for Disease Control and Prevention (CDC), 29 million people in the United States, or 9 percent of the population, have diabetes. Of those, more than a quarter are undiagnosed and not treating their condition.
In type 1 diabetes the body no longer produces insulin because the immune system kills beta cells. In type 2 diabetes, the body develops resistance to insulin. To compensate, beta cells make more of it, which can shorten their lifespan due to fatigue.
Diabetes is typically treated through diet, exercise, blood sugar monitoring, and medication and insulin therapy. While these treatments can be effective at preventing the progression of the disease, they don’t address beta cell production.
The key in treating diabetes in the long term, the Mount Sinai researchers say, is finding ways to increase functioning beta cells, which are often resistant to division and growth.
A Bone Drug for Diabetes?
Vasavada and her colleagues were studying the effects of lactogenic hormones. The pituitary gland creates these hormones, which stimulate lactation and also enhance pancreatic beta cell survival and growth.
When examining proteins inside beta cells that are regulated by these lactogens, the researchers found a bone-related protein called osteoprotegerin, or OPG. OPG is at its highest levels during pregnancy and obesity, suggesting to researchers that they promote beta cell growth. OPG also binds to a protein and receptor pair that affects bone turnover, lactation, and a variety of other functions in the body.
Vasavada and her team found that the protein pair RANKL/RANK inhibits beta cell replication, and that OPG and the drug denosumab reverse this effect to stimulate beta cell production. Denosumab is an antibody that binds to RANKL, inhibiting its action.
The Mount Sinai team has only used the therapy in mice models, but further research may show the drug is a viable therapy for diabetes in humans.
“The findings suggest that there is potential for repurposing this osteoporosis drug for the treatment of diabetes,” Vasavada said.