Diabetes researchers and bioinformaticians from the Icahn School of Medicine at Mount Sinai have developed a new understanding of how human beta cell regenerative drugs work. These drugs, developed at Mount Sinai, may hold promise for the more than 500 million people in the world with diabetes. The results of this study were published this month in Cell Reports Medicine.

Diabetes develops when cells in the pancreas known as beta cells become unable to produce insulin, a hormone that is essential to regulating blood sugar levels. While great progress has been made toward discovering a durable therapy, none are scalable therapeutic options for millions of diabetics across the globe.

For more than 15 years, researchers at the Icahn School of Medicine at Mount Sinai have worked tirelessly to find a solution to cure diabetes by identifying a drug that could make human beta cells regenerate.

In 2015, Mount Sinai researchers discovered the first such drug, called harmine. Harmine is a member of a class of drugs called DYRK1A inhibitors. In 2019 and 2020, the researchers reported that DYRK1A inhibitors can synergise with TGF-beta signalling as well as GLP-1 receptor agonist (GLP-1RA) drugs such as semaglutide (e.g., Ozempic) and exenatide (Byetta) to induce more robust levels of human beta cell regeneration. Finally, in July 2024, they showed that harmine alone increases human beta cell mass by 300%, and if a GLP-1RA is added, by 700%.

A key question has been how harmine causes beta cells to regenerate. In the newest study, the research team reports that the new, regenerated beta cells may be coming from an unexpected source: a second pancreatic cell type called alpha cells. Since alpha cells are abundant in people with type 1 and type 2 diabetes, they may be able to serve as a source for new beta cells in both common types of diabetes.

"This is an exciting finding that shows harmine-family drugs may be able to induce lineage conversion in human pancreatic islets," says Esra Karakose, Ph.D., Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai and corresponding author of the study. "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."

"It has been remarkable and rewarding to watch this multi-group story unfold over the past 15 years," added Andrew F. Stewart, MD, Irene and Dr. Arthur M. Fishberg Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Mount Sinai Diabetes, Obesity, and Metabolism Institute.

He and Peng Wang, Ph.D., Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai, conceived of and performed the initial high-throughput drug screen that led to the discovery of harmine, described in Nature Medicine in 2015.

"A simple pill, perhaps together with a GLP1RA like semaglutide, is affordable and scalable to the millions of people with diabetes," said Dr. Stewart. The Mount Sinai team is moving these studies to human trials.