Researchers have uncovered a new mechanism of action of metformin, one of the most widely used drugs for treating type 2 diabetes, and its effect on the brain.
This comes after a study showed that the drug not only works through the liver and intestines to lower blood sugar levels, but also affects a specific area of the brain. This discovery could change how researchers understand the effects of metformin and could help in the future to develop more precise treatments for diabetes.
Metformin has been used for years to help the body control blood sugar levels and improve its response to insulin. It was previously believed that the anti-diabetic drug's effect was primarily linked to what happens in the liver and intestines, but researchers at Baylor College of Medicine in the United States have found an additional pathway in the brain involved in this effect.
The study found that metformin activates a type of nerve cell known as SF1 in the hypothalamus, while simultaneously inhibiting the activity of a protein called Rap1. This protein plays a role in regulating how the body deals with glucose.
The researchers pointed out that metformin's ability to lower blood sugar levels appears to depend on inhibiting Rap1 activity in this area of the brain.
Dr. Makoto Fukuda, assistant professor of pediatrics and nutrition at Baylor College of Medicine, said that SF1 neurons are activated when metformin reaches the brain, indicating their direct involvement in the drug's effect.
Fukuda explained that the results change the previous understanding of how metformin works, noting that the brain can respond to much lower concentrations of the drug compared to the liver and intestines.
In their experiments, the researchers relied on genetically modified diabetic mice, and found that injecting metformin directly into the brain led to a significant decrease in blood sugar levels, despite using a dose thousands of times lower than the dose given orally.
Researchers believe that understanding this neural pathway may pave the way in the future for the development of drugs that target the mechanism of blood sugar regulation more precisely, as well as help to explain some aspects that have remained unclear in the way metformin works.
It is worth noting that millions of people around the world rely on metformin to control their blood sugar levels. It is primarily used to treat type 2 diabetes, and may also be prescribed in some cases for prediabetes, gestational diabetes, and polycystic ovary syndrome (PCOS).
Metformin is not usually associated with weight gain, compared to some other diabetes medications, but it may cause some side effects, most notably nausea, vomiting, diarrhea, stomach pain, loss of appetite, and a metallic taste in the mouth.
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