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.
Paper Summary
Methodology
The study investigated whether specific drugs could stimulate the transformation of alpha cells in the human pancreas into insulin-producing beta cells, which are vital for managing blood sugar levels. Researchers treated human pancreatic islets (groups of cells containing insulin-producing beta cells) with small-molecule drugs known to affect cell growth and gene expression. They used advanced tools like single-cell RNA sequencing to observe how individual cells responded to the treatments. This process helped identify specific types of alpha cells that might change into beta cells after treatment.
Key Results
The research found that some alpha cells called “cycling alpha cells,” responded strongly to the drugs. These cells showed signs of becoming more like beta cells, which are crucial for producing insulin. The drugs not only increased the number of these cycling alpha cells but also triggered them to take on beta cell characteristics, such as producing insulin-related markers. This suggests that the drugs might help replenish beta cells, potentially aiding diabetes treatment.
Study Limitations
The study only included a small number of human islet donors, which might affect how universally applicable the findings are. The experiments were conducted in a laboratory setting, which might not fully replicate what happens inside a living body. Researchers couldn’t confirm the precise lineage of the alpha cells due to technical constraints, such as the lack of tools to track cell transformations in humans over time. The long-term survival and stability of the newly formed beta cells weren’t studied. There’s uncertainty about how the drugs trigger alpha cells to start resembling beta cells.
Discussion & Takeaways
This study opens up exciting possibilities for treating diabetes. If cycling alpha cells can reliably transform into beta cells, it could provide a way to restore lost insulin production in diabetic patients. This approach might even work for individuals with little to no remaining beta cells, as it doesn’t depend on regenerating existing ones. However, more research is needed to confirm these findings in real-world settings and to refine the drugs to ensure they are safe and effective for long-term use.
Funding & Disclosures
The research was funded by the National Institutes of Health, the National Institute of Diabetes Digestive and Kidney Disease, By BreakthroughT1D, formerly JDRF, as well as through additional generous philanthropic gifts. The authors disclosed potential conflicts of interest, including patents filed by the Icahn School of Medicine at Mount Sinai related to this research and consulting roles with pharmaceutical companies, including Sun Pharmaceutical Industries.
Credit: StudyFinds