RED blood cells (RBC) serve as a primary glucose sink during hypoxia, a 2026 study has found.
RBCs were found to act as glucose regulators, opening doors for novel diabetes treatment strategies.
This follows established findings that altitude reduces the risk of diabetes.
Altitude and Diabetes
Decreased incidence of diabetes and improved glycaemic control at high altitude has been established by several cross-species observations.
In low-oxygen conditions, RBCs can shift their metabolism to absorb sugar from the bloodstream.
In turn, they can deliver oxygen around the body more quickly, and blood sugar levels are lowered.
Between the 1920s and 1940s, the Harvard Fatigue Laboratory studied human physiology under extreme environmental conditions relevant for soldiers during wartime.
Researchers observed improved glucose tolerance in healthy volunteers who were transported to the Chilean Andes at altitudes of up to 6,000 metres.
RBCs as a Glucose Sink
Hypoxia alone was found to robustly improve glucose tolerance and the effect persisted for weeks after return to normal oxygen levels.
PET/CT imaging suggested some glucose sink beyond major internal organs.
In low-oxygen conditions, mice produced significantly more RBCs, and glucose uptake per RBC in vivo also increased. This further contributed to the improved glucose tolerance observed during hypoxic exposure.
Manipulation of RBC numbers directly altered blood glucose, leading researchers to identify hypoxia-induced RBCs as the primary glucose sink.
Generalisability and Molecular Mechanisms
Only young male mice were studied, limiting generalisability.
Whilst researchers evidenced that upregulation of glucose transporters is specific to hypoxia-induced RBCs, the molecular mechanism by which this occurs was not found.
Novel Treatments
Researchers tested a drug they developed, a small-molecule hypoxia mimetic: HypoxyStat.
It successfully rescued hyperglycaemia in mouse models of Type 1 and Type 2 diabetes. The therapy completely abolished high-fat diet induced hyperglycaemia in diabetic mice.
After identifying RBCs as key regulators of systemic glucose metabolism, findings highlighted HypoxyStat as a novel therapeutic approach for hyperglycaemic disorders
References
Martí-Mateos Y et al. Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude. Cell Metab. 2026;DOI:10.1016/j.cmet.2026.01.019.
Forbes WH. Blood sugar and glucose tolerance at high altitudes. AJPH-LC. 1936;116(2):309-316.
