A study has shown that metformin lowers glucose levels not only through the liver and intestines, but also by directly acting on the brain.
A new study by scientists at Baylor College of Medicine in the U.S. has revealed that the anti-diabetic drug metformin, used for over 60 years to treat type 2 diabetes, has a direct effect on the brain. This discovery could lead to the development of new therapies.
Previously, it was believed that metformin lowered blood glucose by reducing its production in the liver and acting through the intestines. The new research shows that the drug also affects the ventromedial hypothalamus (VMH) in the brain, where it blocks the protein Rap1, which regulates glucose metabolism.
Experiments on mice demonstrated that direct injections of metformin into the brain lowered blood sugar levels. In mice without Rap1, the drug had no effect, although other anti-diabetic drugs still worked. Researchers also identified that SF1 neurons are involved in how metformin works.
“This discovery changes our understanding of metformin,” said Professor Makoto Fukuda. “The drug acts not only on the liver and intestines but also directly on the brain, and the brain responds to much lower concentrations.”
A deeper understanding of metformin’s mechanism of action could, in the future, allow for enhancing its effects, making diabetes treatment more targeted, and potentially even using the drug to slow brain aging and increase lifespan.
The study was published in the journal Science Advances.
