Metformin has been the standard treatment for type 2 diabetes for more than six decades, yet scientists have never fully understood how it lowers blood sugar. Now, researchers at Baylor College of Medicine and collaborators around the world have identified an unexpected factor behind its effects: the brain. Their findings reveal a previously unknown brain pathway involved in metformin's anti-diabetic action, opening the door to more precise and effective treatments. The study appeared in Science Advances.
"It's been widely accepted that metformin lowers blood glucose primarily by reducing glucose output in the liver. Other studies have found that it acts through the gut," said corresponding author Dr. Makoto Fukuda, associate professor of pediatrics -- nutrition at Baylor. "We looked into the brain as it is widely recognized as a key regulator of whole-body glucose metabolism. We investigated whether and how the brain contributes to the anti-diabetic effects of metformin."
The Brain's Role in Blood Sugar Control
The researchers focused on a protein called Rap1, located in a region of the brain known as the ventromedial hypothalamus (VMH). They found that metformin's ability to lower blood sugar at clinically relevant doses depends on suppressing Rap1 activity in this area.
