Daijiworld Media Network - New Delhi

New Delhi, Mar 27: A new study has identified a brain-related pathway through which Metformin regulates blood sugar, challenging long-held beliefs about how the widely used diabetes medication works.

For over six decades, metformin has been considered to primarily lower blood glucose by reducing production in the liver, with some studies also pointing to its action in the gut. However, researchers from Baylor College of Medicine have now found that the brain also plays a crucial role in its anti-diabetic effects.

Lead author Makoto Fukuda said the team explored the brain’s involvement, given its key role in regulating whole-body glucose metabolism. The findings, published in Science Advances, suggest that metformin has been influencing brain pathways all along.

The study focused on Rap1, a protein located in the brain’s ventromedial hypothalamus, an area critical for sensing glucose and controlling satiety. Researchers found that suppressing Rap1 activity enabled metformin to significantly reduce blood sugar levels.

Experiments on genetically modified mice lacking Rap1 showed that low doses of metformin failed to improve blood sugar levels, although other treatments like insulin remained effective. However, when metformin was directly delivered to the brain—even at extremely low doses—it led to a marked reduction in blood glucose.

Further analysis revealed that specific brain cells known as SF1 neurons were activated by metformin, but only when Rap1 was present. In its absence, the drug had no effect, confirming the protein’s essential role in this newly discovered pathway.

The findings suggest that the brain is highly sensitive to metformin, responding to much lower concentrations than the liver or intestines.

Researchers said the discovery could pave the way for more targeted diabetes treatments focused on brain pathways, potentially improving effectiveness and reducing required dosages.