Doctors have relied on metformin to treat type 2 diabetes for generations, yet one basic question has remained unanswered: exactly how does the medicine lower blood sugar?
A new international study led by Baylor College of Medicine suggests the answer may lie inside the brain.
The research, published in Science Advances, challenges the long-held belief that metformin works mainly in the liver and digestive system.
The researchers examined a protein called Rap1 in an area of the brain known as the ventromedial hypothalamus.
This region helps control how the body uses energy and keeps blood sugar within a healthy range. They discovered that metformin switches down Rap1 activity, allowing blood sugar levels to improve.
To confirm the finding, the scientists studied diabetic mice that lacked Rap1 in this brain region. Unlike normal mice, these animals gained little benefit from low doses of metformin. Other diabetes medicines, including insulin and GLP-1 drugs, still reduced blood sugar, showing that the newly discovered pathway is unique to metformin.
The team also tested whether metformin could work directly inside the brain. They injected very small amounts of the medicine into diabetic mice. Despite using doses far below those taken by mouth, the treatment still produced a strong reduction in blood sugar levels.
Further experiments showed that metformin activates SF1 nerve cells in the brain. However, this only happened when Rap1 was present. Without the protein, the brain cells failed to respond, proving that Rap1 is essential for this newly discovered mechanism.
This discovery could have important medical benefits. If scientists can design medicines that target this brain pathway more precisely, future treatments might control blood sugar more effectively while reducing unwanted side effects. The research may also help explain why metformin has been linked to other possible health benefits, including effects on brain aging.
The researchers plan to investigate whether the same brain pathway is responsible for these additional benefits. Understanding this connection could lead to new treatments not only for diabetes but also for other conditions involving brain health and metabolism.
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For more health information, please see recent studies that low calorie diets may help reverse diabetes, and 5 vitamins that may prevent complication in diabetes.
Source: Baylor College of Medicine.
