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Metformin Lowers Blood Sugar Through Brain Circuit, Mouse Study Finds

The findings suggest drugmakers could target Rap1 in the ventromedial hypothalamus for sharper glucose control.

Overview

  • A Baylor-led team reported in Science Advances this week that metformin acts in the brain’s ventromedial hypothalamus to lower blood sugar by suppressing a protein called Rap1.
  • Mice engineered to lack Rap1 in that brain region did not benefit from low-dose metformin, though insulin and GLP-1 agonists still reduced glucose.
  • Very small amounts of metformin delivered into the brain cut blood sugar at doses thousands of times lower than standard oral amounts, showing the brain’s high sensitivity to the drug.
  • Electrophysiology tests found the drug activates SF1 neurons only when Rap1 is present, linking the protein to neural control of glucose.
  • Scientists say the work points to brain-targeted diabetes therapies and may relate to reported brain benefits of metformin, though human studies are still required before clinical use.