New diabetes drug boosts insulin production by 700%

Diabetes is one of the most common chronic illnesses in the world, affecting more than 10 percent of adults. At the root of both type 1 and type 2 diabetes is a shortage of insulin-producing β cells in the pancreas. These cells regulate blood sugar, and once they are lost, no current treatment is able to replace them. Medications help people manage glucose, but they don’t create new β cells.

Now, an international team of researchers has found a way to change that. By pairing two drugs—harmine, a compound that blocks an enzyme called DYRK1A, and exendin-4, a GLP-1 receptor agonist already used in diabetes therapy—they showed for the first time that human β cell numbers can multiply inside a living system.

This discovery has been years in the making. The work began in 2015 at the Icahn School of Medicine at Mount Sinai under physician-scientist Andrew F. Stewart, MD. He and Peng Wang, PhD, first screened thousands of chemicals to see if any could push human β cells to divide. Their search led to harmine, a natural molecule found in certain plants.

The next step was taken by Adolfo Garcia-Ocaña, PhD, at City of Hope in Los Angeles. His team transplanted small groups of human pancreatic islets into mice lacking immune defenses, a standard model for both type 1 and type 2 diabetes. Over three months, mice treated with harmine and exendin-4 showed a staggering 700 percent increase in human β cell volume.

“This is the first time scientists have developed a drug treatment proven to increase adult human β cell numbers in vivo,” Garcia-Ocaña said. “This research brings hope for future regenerative therapies to potentially treat the hundreds of millions of people with diabetes.”

To be sure the cells had really multiplied, the team turned to Sarah A. Stanley, MBBCh, PhD, at Mount Sinai. She used iDISCO+, a laser-based imaging technique that makes tissue clear so it can be studied in 3D. This technology revealed not only that β cell mass had expanded four- to sevenfold, but also why. The cells weren’t just dividing more often—they were also dying less, leading to a lasting increase in overall mass.

One month after the drugs were stopped, the larger β cell population remained, although cell division slowed. The effect proved robust across donor samples of different ages and health backgrounds, suggesting it could apply broadly.

The bigger β cell pools weren’t just sitting idle. Treated mice produced more human insulin, had better glucose tolerance, and showed stronger insulin secretion when challenged with sugar. Importantly, the cells still carried markers of healthy, mature β cells.

The therapy also helped with one of the biggest challenges in islet transplantation: survival. Normally, a large fraction of β cells die shortly after grafting. When harmine and exendin-4 were given right after surgery, far fewer cells were lost. Early on, the drugs activated a gene called VGF, which helps protect cells and improve survival. When VGF was blocked, the benefits disappeared, showing its key role in the process.

The researchers checked organs like the liver, lungs, brain, and heart to see if the drugs triggered unwanted growth. Other than mild effects in the lungs linked to exendin-4, no abnormal tissue changes appeared. Equally important, the drugs did not enlarge α cells, which make glucagon, another key hormone in blood sugar control.

Andrew Stewart noted how far the work has come. “The steady progression from the most basic human β cell biology, through robotic drug screening, and now moving to human studies, illustrates the essential role for physician-scientists in academia and pharma,” he said.

Mount Sinai has already run a phase 1 clinical trial of harmine in healthy volunteers to test safety. Robert J. DeVita, PhD, has designed next-generation DYRK1A inhibitors that may be even safer and more selective. First-in-human trials combining these drugs with GLP-1 receptor agonists are planned for the near future.

One challenge remains for type 1 diabetes: the immune system’s attack on new β cells. At City of Hope, Garcia-Ocaña and colleague Alberto Pugliese, MD, are preparing to pair β cell regeneration therapies with drugs that calm immune responses. Their aim is to protect new cells long enough to restore insulin production.

“This is very exciting because there is nothing like this available to patients right now,” Garcia-Ocaña said.

The project has been backed by the National Institutes of Health, BreakthroughT1D, the Wanek Family Project for Type 1 Diabetes at City of Hope, and philanthropic donations. The findings were published in Science Translational Medicine.

This study marks the first real evidence that human insulin-producing cells can be regenerated in living systems through a drug treatment. If future clinical trials succeed, this therapy could provide a breakthrough option for people with diabetes, potentially reducing or even eliminating the need for constant insulin injections.

By restoring the body’s own ability to produce insulin, patients could enjoy better long-term health, fewer complications, and an improved quality of life.

The research also opens doors for combining regenerative therapies with immune-modulating drugs, offering hope for tackling type 1 diabetes more directly.

Note: The article above provided above by The Brighter Side of News.

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