Diabetes, a chronic disease that needs to be managed with medication and lifestyle changes, affects about 830 million people worldwide and is one of the fastest-growing illnesses globally. A groundbreaking breakthrough in diabetes research may soon transform its treatment for millions worldwide. Scientists are working on a revolutionary pill that could

cure diabetes

by addressing the root causes of the disease.
Researchers at Mount Sinai have moved one step forward in making this pill a reality which can reprogram the body to make

insulin-producing cells

again.
Diabetes develops when beta cells in the pancreas are not able to produce insulin, an essential hormone for blood sugar management. In both

Type 1 and Type 2 diabetes

, patients report a significant reduction in active insulin-producing beta cells. Until now, the medications are used to manage diabetes symptoms, but now researchers are looking for ways to replenish and revive these crucial beta cells that can start producing insulin again.

How Harmine can help regenerate insulin-producing cells

Back in 2015, the researchers at Mount Sinai identified harmine, a drug belonging to DYRK1A inhibitors, the compound capable of activating insulin-producing human

beta cell regeneration

.
Building on their earlier findings, the research team made significant progress in 2019 and 2020, discovering that harmine could work in synergy with

GLP-1 receptor agonists

such as semaglutide and exenatide to boost beta cell regeneration.

By July 2024, their studies revealed groundbreaking results: harmine alone increased human beta cell mass by 300%, and when paired with a GLP-1 receptor agonist like Ozempic, that growth skyrocketed to an impressive 700%.

In an exciting discovery, researchers found that alpha cells, another kind of pancreatic cell which are found 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.”

How the experiment was carried out

Using single-cell RNA sequencing technology, researchers examined the genetic activity of more than 109,881 individual cells from human pancreatic islets donated by four adults. This advanced technique provided detailed insights, revealing that “cycling alpha cells” might have the ability to convert into insulin-producing beta cells. Since alpha cells are the most abundant cell type in pancreatic islets, they could become a crucial source for generating new beta cells if the transformation process can be effectively managed.

The Mount Sinai team is now set to move to 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.
The study was published in the journal Cell Reports Medicine.