After 60 years, scientists discover metformin works in the brain to control blood sugar

Scientists have discovered metformin lowers blood sugar by acting in the brain. It reveals a previously unknown pathway that could reshape future diabetes treatment and research.

Metformin.

Metformin has been used as the first-line drug to treat type 2 diabetes for over 60 years but it has long been thought that its effects were primarily due to its ability to inhibit glucose production in the liver or to affect the gut. A new study now shows that the popular medication has a direct effect in the brain to regulate blood sugar. The results published in the journal Science Advances led by researchers from Baylor College of Medicine identified that there is a protein named Rap1 in a specific region of the brain called the ventromedial hypothalamus (VMH) which is suppressed by metformin to regulate the body's glucose metabolism.

How does metformin work in the brain?

The brain is known to be an important regulator of whole-body glucose metabolism so a team of scientists investigated if the brain played a role in metformin's anti-diabetic effect. What is interesting about these findings is that researchers found a key protein that was important for the activity called Rap1. When they performed their experiments researchers discovered that the blood sugar lowering effect of metformin at clinically relevant doses relies on shutting off the activity of Rap1 in the VMH of the brain.

What did the study find?

To better understand how this works researchers employed genetically modified mice which lacked the protein in their VMH and fed them a high-fat diet to mimic type 2 diabetes. The findings revealed:

1. Low dose metformin treatment did not affect mice lacking Rap1
2. They had elevated blood sugar levels even after taking the medication
3. Other diabetes medications such as insulin and GLP-1 receptor agonists were still effective
4. This indicates that the role of Rap1 is unique in the glucose-lowering effect of metformin

Metformin: brain's extreme sensitivity to the action of this drug

The scientists also injected a very small amount of metformin directly into the brain of the diabetic mice. Infact significantly less than the dose administered orally markedly lowered blood sugar demonstrating the brain's extreme sensitivity to the action of this drug. Another key player identified in the study was SF1 neurons in the VMH. The researchers discovered that the electrical activity of these neurons was enhanced by metformin only in the presence of Rap1.

Researchers say the results could lead to a change in diabetes treatment in the future. The research reveals a whole new mechanism of action for one of the most common diabetes drugs in use around the world. The findings have broadened the field of research on how metformin regulates blood sugar by demonstrating that it directly affects the brain via the Rap1 pathway. Regardless it is important to note that the results are preliminary from animal studies and should be confirmed in human drug trials but they do offer a basis to create new-generation drugs to treat diabetes that may be more effective and targeted.

Disclaimer: This article is for informational purposes only and is not medical advice. Consult a qualified healthcare professional before making lifestyle or treatment decisions based on these findings.