Rare benign tumors hold clues to treating diabetes

How to do that effectively has, of course, been the challenge.

Now, though, there might be a new breakthrough, with researchers having discovered that insulinomas—a kind of rare benign tumor—are a potential “map” to learning how to regenerate insulin-producing cells. This is because insulinomas contain, as the Icahn School of Medicine at Mount Sinai puts it, “a complicated wiring diagram for regeneration of insulin-producing human beta cells, which may hold the key to diabetes drug development.” The study, titled “Insights into Beta Cell Regeneration for Diabetes via Integration of Molecular Landscapes in Human Insulinomas,” was published online recently in Nature Communications.

With the help of an international group of investigators, the Mount Sinai team collected 38 human insulinomas—rare pancreatic tumors that secrete too much insulin—and analyzed their genomics and expression patterns.

“For the first time, we have a genomic recipe—an actual wiring diagram in molecular terms that demonstrates how beta cells replicate,” said Dr. Andrew Stewart, director of the Diabetes, Obesity, and Metabolism Institute at the Icahn School of Medicine and lead author of the study. “When you think of tumor genomics, you’re thinking of breast cancer or colon cancer, leukemia, etc. No one is thinking of doing genomics on tumors that don’t really kill people. So the real innovation here is that we collected benign tumors that don’t metastasize and don’t cause great harm, and we’re trying to use these benign tumors that have beta cell regeneration going on in them, as the only reasonable source of genomic information on how to make beta cells regenerate.”

Knowing where to look is one thing, but in the era of big data, knowing how to look is very important, too, said Dr. Carmen Argmann, associate professor of genetics and genomic sciences at the Icahn School of Medicine and co-author of the paper. “In this case, we looked at millions of data points collected in rare human insulinomas to try and find an answer to a common disease, diabetes. We then computationally created two molecular pictures from that data, one from the insulinoma and one for the normal beta cell, and identified the critical differences that will hopefully lead to new ways to expand beta cell mass in diabetes patients. We plan to explore clinical applications of these new findings in close collaboration with the team at Sema4, a company specializing in big data analytics for diagnostic development.”

This isn’t the first time Stewart has seen progress in producing beta cells. In fact, just a couple years ago, he and his team published a paper in Nature Medicine showing that the drug harmine drove the sustained division and multiplication of adult human beta cells. Granted, it was in culture and not in people, but still an achievement that had eluded researchers for years, according to Icahn. Stewart and his team also reported that harmine treatment tripled the number of beta cells and led to better control of blood sugar in three groups of mice engineered to mimic human diabetes.

According to Stewart, the results of the harmine study provided a large body of evidence demonstrating that the harmine drug class can make human beta cells proliferate at levels that may be relevant for diabetes treatment. While harmine may be one path to beta cell regeneration, the more recent study results suggest that a number of other biological pathways might be treatable with novel diabetes drugs and that regenerating or increasing beta cells in vivo for humans might not be so unachievable soon.

“We are excited and gratified by these remarkable results, which reveal an extraordinary array of new and validated pathways for diabetes drug development,” said Dr. Dennis S. Charney, the Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine. “In a very short time, we have made terrific progress, and it is really a credit to the remarkably diverse areas of strength in biomedical research at Mount Sinai. It is truly an exciting set of discoveries for the field of diabetes.”