Rare Tumor May Point the Way to Diabetes Treatment
THURSDAY, Oct. 5, 2017 -- A rare, benign tumor that grows in the pancreas may give doctors the tools they need to help people with diabetes make more insulin.
These tumors are called insulinomas because they secrete the hormone insulin in excessive amounts. People with diabetes don't have enough insulin to cover their bodies' basic needs for the hormone.
The researchers thought by mapping the genetic makeup of insulinoma tumors, they might come up with the genomic recipe for regenerating the beta cells that produce insulin. And if they could use that "recipe" to make a drug that would trigger the body to make insulin, they could treat -- or possibly even reverse -- diabetes.
The study's senior author, Dr. Andrew Stewart, said the researchers have mapped approximately 90 insulinoma tumors at this point, but only 38 were included in the current study.
"We have an actual wiring diagram in molecular terms for beta cell replication, and there are different mutation patterns that lead to beta cell regeneration. We've found about 30 different pathways," said Stewart.
He directs the Diabetes, Obesity and Metabolism Institute at the Icahn School of Medicine at Mount Sinai in New York City.
Stewart said it wasn't a complete surprise to see that there were multiple pathways, instead of just one or two. For example, he said, there isn't just one set of molecules that makes growth plates during childhood.
"We found many additional pathways... This is a data mine for diabetes researchers," he said.
Insulin, which is made in the pancreas, is used to usher the sugar from foods into the body's cells to be used as energy.
People with type 2 diabetes are resistant to the effects of insulin, and may not make enough insulin. About 29 million people in the United States have this type of diabetes, which is associated with obesity and a sedentary lifestyle.
Type 1 diabetes is an autoimmune disease that causes the body to mistakenly destroy insulin-producing beta cells. People with type 1 diabetes must replace that lost insulin through injections or an insulin pump. Approximately 1.25 million Americans have type 1 diabetes, according to the American Diabetes Association.
With the information from this new study, the researchers hope to find or develop drugs that could work on one of those newly identified pathways. But it's important that the pathway doesn't have any other serious effects.
Stewart and his colleagues published a study in Nature Medicine in 2015 showing how the drug harmine could prompt beta cell regeneration in the lab and in mice. The pathway linked to harmine was one of the ones found in the current paper, too.
But "harmine is a hallucinogen," Stewart said.
So, if taken as a pill or given as a shot, it would affect the whole body and produce unwanted side effects.
"We still need a way to deliver it specifically to the beta cells," said Stewart.
There's also a concern that a drug like an insulinoma could cause the body to produce too much insulin, leading to potentially dangerous side effects.
Andrew Rakeman is assistant vice president of research for JDRF -- formerly the Juvenile Diabetes Research Foundation.
"You don't want to replicate the lack of control of an insulinoma. The question is can we find ways to switch these pathways on and then switch them off?" said Rakeman, who wasn't involved in the new study.
He also pointed out that it's important that any drug just targets the beta cells and doesn't encourage cell growth in other areas.
Stewart said a therapy developed from these pathways would likely be for people with type 2 diabetes first. People with type 1 diabetes have the added issue of the autoimmune attack, which could destroy any newly made cells.
For people with type 1 diabetes, some sort of immune system suppression might be necessary, Stewart said. Rakeman said it's possible repeated treatments might keep enough beta cells alive to be effective, though that remains to be seen.
For now, Stewart and Rakeman said these findings are hopeful.
"Amazing things are happening in the world of beta cell regeneration," Stewart said.
Rakeman agreed. "We understand much more about what's happening with beta cells. We can take those lessons and build out therapeutic targets," he said.
The study was published Oct. 3 in the journal Nature Communications.
The American Association of Endocrine Surgeons has more on insulinomas.
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Posted: October 2017