Imagine a world where diabetes could be treated with a simple pill that essentially reprograms your body to produce insulin again. Researchers at Mount Sinai have taken a significant step toward making this possibility a reality, uncovering a groundbreaking approach that could potentially help over 500 million people worldwide living with diabetes.
Diabetes, affecting 537 million people globally, develops when cells in the pancreas known as beta cells become unable to produce insulin, a hormone essential for regulating blood sugar levels. In both Type 1 and Type 2 diabetes, patients experience a marked reduction in functional, insulin-producing beta cells. While current treatments help manage symptoms, researchers have been searching for ways to replenish these crucial cells.
The journey to this latest discovery began in 2015 when Mount Sinai researchers identified harmine, a drug belonging to a class called DYRK1A inhibitors, as the first compound capable of stimulating insulin-producing human beta cell regeneration. The research team continued to build on this foundation, reporting in 2019 and 2020 that harmine could work synergistically with other medications, including GLP-1 receptor agonists like semaglutide and exenatide, to enhance beta cell regeneration.
In July 2024, researchers reported remarkable results: harmine alone increased human beta cell mass by 300 percent in their studies, and when combined with a GLP-1 receptor agonist like Ozempic, that increase reached 700 percent.
However, there’s an even more exciting part of this discovery. These new cells might come from an unexpected source. Researchers discovered that alpha cells, another type of pancreatic cell that’s abundant in both Type 1 and Type 2 diabetes, could potentially be transformed into insulin-producing beta cells.
“This is an exciting finding that shows harmine-family drugs may be able to induce lineage conversion in human pancreatic islets,” says Dr. Esra Karakose, Assistant Professor of Medicine at Mount Sinai and the study’s corresponding author, in a statement. “It may mean that people with all forms of diabetes have a large potential ‘reservoir’ for future beta cells, just waiting to be activated by drugs like harmine.”
Using single-cell RNA sequencing technology, the researchers analyzed over 109,881 individual cells from human pancreatic islets donated by four adults. This technique allowed them to study each cell’s genetic activity in detail, suggesting that “cycling alpha cells” may have the potential to transform into insulin-producing beta cells. Alpha cells, being the most abundant cell type in pancreatic islets, could potentially serve as an important source for new beta cells if this transformation process can be successfully controlled.
The Mount Sinai team is now moving these studies toward human trials.
“A simple pill, perhaps together with a GLP1RA like semaglutide, is affordable and scalable to the millions of people with diabetes,” says Dr. Andrew F. Stewart, director of the Mount Sinai Diabetes, Obesity, and Metabolism Institute.
While the research is still in its early stages, it offers hope to millions of people who currently manage diabetes through daily insulin injections or complex medication regimens. The possibility of a treatment that could essentially restart the body’s insulin production is nothing short of revolutionary.
The study, published in the journal Cell Reports Medicine, represents a significant step forward in diabetes research. By potentially turning one type of pancreatic cell into another, researchers may have found a way to essentially reprogram the body’s own cellular mechanisms to combat diabetes.