- A recent study in mice found that a combination of the two drugs could effectively reverse diabetes.
- The drug works by “regenerating” the cells in the pancreas that produce insulin.
- In just three months, the number of these cells increased by up to 700%.
- Although more research is needed, the results are promising.
The new study Science Translational MedicineInvestigating experimental drug combinations for the treatment of type 1 and type 2 diabetes.
The treatment increased the number of insulin-producing cells by up to seven-fold and also improved the animals’ blood sugar control, according to the paper.
The two drugs are exendin-4, a GLP1 receptor agonist commonly prescribed for diabetes, and harmine, which inhibits an enzyme called dual tyrosine-regulated kinase 1A (DYRK1A).
Scientists need to do more studies to confirm these benefits, but the authors are excited about the prospect.
Because patients with diabetes often already take GLP1 receptor agonists, adding a DYRK1A inhibitor could be a “simple, inexpensive, and scalable approach to diabetes treatment,” the authors explain.
Although effective diabetes medications exist, none can help restore beta cells.
Today’s Medical News I spoke with one of the authors of the new study. Dr. Adolfo Garcia OcañaProfessor and Chair of the Department of Molecular and Cellular Endocrinology at City of Hope, California.
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Beta cell proliferation is the process by which beta cells divide and increase in number.
Other studies have also shown that DYRK1A inhibitors can increase beta cell numbers through a second mechanism. DifferentiationHere, stem cell-like progenitor cells are transformed into fully functional beta cells.
Thus, DYRK1A inhibitors have a two-pronged approach: they allow precursor cells to fully develop into beta cells, and they promote the division and proliferation of existing beta cells.
While this seems promising, the authors of the new study say, “whether this would translate into a clinically meaningful increase in beta cell mass in humans remains questionable.”
There are several other open questions. For example, scientists don’t know whether DYRK1A inhibitors would help improve beta cell survival. That’s an important question: If beta cells divided more rapidly, there would be little benefit if they didn’t survive.
Similarly, it is not clear whether these drugs can improve the blood supply to the islets of Langerhans, another important question. evidence It has been suggested that restricting the blood supply to the islets may inhibit insulin release from the beta cells and may also impair islet survival.
To test whether the DYRK1A inhibitor harmine and the GLP-1 agonist exendin-4 support beta cell health, the scientists turned to a mouse model: They transplanted human pancreatic islets containing beta cells into the kidneys of live mice that lack an immune system.
Scientists fed mice harmine and exendin-4 for three months, and the results were a significant increase in beta cell numbers, improved beta cell function, and improved blood sugar control.
García Ocaña said this combined effect of increasing proliferation and differentiation was “an aspect not seen with any of the drugs tested so far,” and that “the therapeutic implications of this drug combination in the treatment of diabetes are significant.”
There were also “hints” that this drug combination might enhance the blood supply to the islets, which the authors believe may be a driving force behind the beta-cell increase.
The scientists measured these effects in mice with normal blood sugar levels and in mice with “severe diabetes” – and importantly, the mice did not experience potentially fatal hypoglycemia (low blood sugar levels).
MNT Contact us Karel Le Roux, MBChB, MSC, FRCP, FRCPath, PhDHe is a Specialist Advisor to Lindas Health and Director of the Metabolic Medicine Group at University College Dublin, Ireland.
“Combining a DYRK1A inhibitor with exendin-4 increased human beta cell mass four- to seven-fold in diabetic and non-diabetic mice over a three-month period and reversed diabetes,” said Le Roux, who was not involved in the study.
“This is the first time scientists have developed a drug treatment proven to increase the number of beta cells in adult humans,” García Ocaña said. “This research has the potential to one day use regenerative medicine to treat the hundreds of millions of people with diabetes.” press release.
Le Roux is also optimistic about the future.
“If these results are demonstrated in humans, they may help patients with early signs of beta cell failure and could also transform the care of patients with type 1 diabetes and those at risk of type 2 diabetes.”
The results are certainly promising, but there’s still a long way to go. First, what happens in mice doesn’t necessarily happen in humans.
And because this is an entirely new approach, it’s not clear how much beta cell regeneration and proliferation is needed to make a meaningful difference in people with diabetes.
However, the authors write, “the four- to seven-fold increase in human beta cell mass over a three-month period and the normalization of glycemic control without hypoglycemia as shown here in the diabetic state are encouraging.”
Another concern is that DYRK1A inhibitors may have unexpected effects on other organs. DYRK1A receptors are widely distributed throughout the body. According to García-Ocaña, “DYRK1A is a key protein that controls many aspects of cellular life, and its dysregulation can lead to pathological processes.”
Garcia Ocaña said: MNT “How we limited undesirable effects on other parts of the body by using DYRK1A inhibitors at very low doses, enhancing safety.”
The scientists also noted that they didn’t see any serious health problems in the mice, but humans are a whole different animal.
Another concern is that there was wide variation in how the mice responded to each individual combination of treatments, meaning that the drug combination may not be effective for some people.
Still, with diabetes now becoming an epidemic, a 700% increase in beta cells is certainly worth following up on. “Phase 1 clinical trials to test the safety and tolerability of harmine and future new DYRK1A inhibitors are ongoing at Mount Sinai in New York,” Garcia-Ocaña said.
He and his colleagues are currently The Wanek Family Project for Type 1 DiabetesBecause type 1 diabetes is an autoimmune disease, the researchers plan to test “inducers of beta cell regeneration along with immunomodulators that regulate the immune system.”
“The goal of this combination is to grow new beta cells and improve insulin levels,” he explained.
If further research confirms these findings, it could be a real breakthrough in diabetes treatment. “Harmine is a natural product found in several plants, so it’s not hard to get hold of,” García-Ocaña said. Combined with growing interest in DYRK1A inhibitors, the drug may be relatively accessible once it hits the market.
But this is “difficult to predict at this point,” he noted.
