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Hypoxia Turns Red Blood Cells Into Glucose Sinks, Pointing to New Diabetes Therapies

By mapping a hypoxia‑triggered switch in red blood cells that shunts glucose into 2,3‑DPG, researchers outline a potential new path for diabetes treatment.

Overview

  • In Cell Metabolism, a Gladstone‑led team reports that low oxygen drives bone marrow to produce more red blood cells that each take up more glucose via increased GLUT1.
  • The glucose is rapidly converted to 2,3‑DPG, improving oxygen release, with the underlying Band 3–hemoglobin displacement of glycolytic enzymes confirmed in mouse and human red blood cells.
  • In mouse diabetes models, three approaches—chronic hypoxia, red blood cell transfusion, and a pill called HypoxyStat—reversed hyperglycemia, with HypoxyStat outperforming existing drugs in those tests.
  • The metabolic benefits from hypoxia persisted for weeks to months after mice returned to normal oxygen levels, indicating durable effects of the red blood cell program.
  • Epidemiological patterns of lower diabetes risk at higher altitudes gain a mechanistic explanation, though the findings remain preclinical and no human trials have been reported.