A team at Baylor College of Medicine has identified a brain-based pathway that plays a significant role in how metformin controls blood glucose. The findings, published in the journal Science Advances, could reshape how scientists develop future diabetes therapies. The research centered on a protein called Rap1, found in a region of the brain known as the ventromedial hypothalamus, or VMH. Researchers found that metformin's ability to lower blood sugar at clinically relevant doses depends on its suppression of Rap1 activity in that specific brain area. To test the connection, the Fukuda lab used genetically engineered mice that lacked Rap1 in the VMH. The animals were placed on a high-fat diet to simulate Type 2 diabetes. When given low doses of metformin, their blood sugar did not improve. Other diabetes treatments, including insulin and GLP-1 agonists, continued to work normally, suggesting the problem was specific to metformin's brain pathway.
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