New Diabetes Drug Combination Induces High Rates of Human Beta Cell Regeneration

When combining a drug that is known to cause beta cells to proliferate with another drug that is already in widespread use in people with diabetes, it will cause the cells to proliferate at a rate of 5% to 6% per day, according to the study authors.

Researchers at the Icahn School of Medicine at Mount Sinai have discovered a novel combination of 2 drug classes that cause the highest rate of proliferation ever observed in adult human beta cells without harming most other cells in the body when together. These data are an important step toward a diabetes treatment that restores the body's ability to produce insulin.

When combining a drug that is known to cause beta cells to proliferate with another drug that is already in widespread use in people with diabetes, it will cause the cells to proliferate at a rate of 5% to 6% per day, according to the study authors.

In type 1 diabetes, the immune system mistakenly attacks and destroys beta cells; this deficiency of functioning beta cells is also an important contributor to type 2 diabetes. In terms of the most recent developments in diabetes research, creating medications that can increase the number of healthy beta cells is the biggest priority.

According to the lead author of the study, Andrew Stewart, MD, director of the Mount Sinai Diabetes, Obesity, and Metabolism Institute, none of the drugs currently on the market can induce beta cell regeneration in people with diabetes. Other researchers in the field are studying pancreatic transplantation, beta cell transplantation, and stem cell replacement of beta cells for people with diabetes; however, none of these approaches is in widespread use.

In a 2015 study by Stewart and his team, the results showed that harmine, a drug that inhibits the enzyme dual specificity tyrosine-regulated kinase 1A (DYRK1A), induced multiplication of adult human beta cells. In addition, the team also discovered that harmine treatment led to normal control of blood sugar and proliferation in human beta cells. Although the discovery was a major advance in diabetes treatment, the proliferation rate was lower than needed to rapidly expand beta cells in people with diabetes.

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In a December 2018 study, Stewart and his team continued to build upon prior research, discovering that DYRK1A inhibitors combined with another drug that inhibits transforming growth factor beta superfamily members (TGFβSF) could cause beta cells to proliferate at a rate of 5% to 8% per day. Even with this rate, TGFβSF would most likely have adverse effects on other organs in the body that would prevent clinical use, according to the authors.

In the February 2020 study, the researchers combined DYRK1A inhibitors, such as harmine, with a class of beta cell-targeting drugs, also known as GLP1R agonists, which are already in widespread use is people with type 2 diabetes. The results showed that in beta cells from people both with and without type 2 diabetes, harmine combined with any of the many GLP1R agonist drugs currently on the market for diabetes yields high rates of human beta cell replication.

“The beauty here is that the combination of DYRK1A inhibitors with GLP1R agonists achieves the highest rate of human beta cell replication possible, and does so in a highly specific way,” said Courtney Ackeifi, postdoctoral fellow in Stewart’s lab and first author of the paper in a prepared statement to Mount Sinai. “This is an important advance in the field of diabetes because we may have found a way to convert a widely used class of diabetes drugs into a potent human beta cell regenerative treatment for all forms of diabetes.”

REFERENCE

Mount Sinai discovers new drug combo to induce high rates of human beta cell regeneration [news release]. New York, NY; Mount Sinai: February 12, 2020. https://www.mountsinai.org/about/newsroom/2020/mount-sinai-discovers-new-drug-combo-to-induce-high-rates-of-human-beta-cell-regeneration-pr. Accessed February 18, 2020.