Metformin affects the brain and helps regulate blood sugar, study finds

Researchers at Baylor College of Medicine report that metformin engages a brain pathway involving the Rap1 protein in the ventromedial hypothalamus, and mice lacking Rap1 in that area did not show blood sugar improvement from low-dose metformin.

Researchers at Baylor College of Medicine report that part of metformin's blood-sugar lowering effect works through a brain pathway. The team published the findings in Science Advances and focused on the Rap1 protein in the ventromedial hypothalamus (VMH). In mice engineered to lack Rap1 in the VMH, low doses of metformin did not improve blood sugar. The researchers also found that tiny amounts of metformin delivered directly into the brain lowered blood sugar, indicating the brain responds at far lower doses than the liver or gut. Key findings: - Metformin's ability to lower blood glucose at clinically relevant doses depended on suppression of Rap1 activity in the VMH in mice. - Mice lacking Rap1 in the VMH did not show blood sugar improvement with low-dose metformin, while insulin and GLP-1 agonists continued to work. - Direct delivery of very small amounts of metformin into the brain lowered blood sugar in diabetic mice. - SF1 neurons in the VMH showed increased electrical activity when metformin was present, and that activity required Rap1. - The study involved collaborators at Louisiana State University, Nagoya University and Meiji University, and was funded by the National Institutes of Health, the American Heart Association, the American Diabetes Association and other foundations. Summary: The study identifies Rap1 signaling in the VMH and activation of SF1 neurons as a brain pathway that contributes to metformin's glucose-lowering effect in mice. The findings could influence how researchers approach the development of future diabetes therapies and prompt further study of whether the same pathway explains other reported effects of metformin, such as possible links to brain aging. Undetermined at this time.