New research published in Cell Metabolism suggests that red blood cells (RBCs) may play a previously unrecognised role in regulating blood glucose levels, a finding with potential implications for diabetes research.
The study was prompted by epidemiological observations that populations living at high altitudes consistently exhibit lower rates of diabetes and improved glucose tolerance than those at sea level. Despite reduced oxygen availability, blood sugar regulation appears enhanced in these communities, a paradox that researchers set out to explain.
Using mouse models exposed to low-oxygen (hypoxic) environments, the research team found that chronic hypoxia rapidly reduced basal blood glucose levels, with improvements in glucose tolerance observed within days and persisting for over a month after animals returned to normal oxygen conditions. Notably, insulin sensitivity did not appear to drive these changes, pointing to an alternative mechanism.
Further investigation identified RBCs as a major contributor. Under hypoxic conditions, RBC production nearly doubled, and individual red blood cells displayed enhanced glucose uptake capacity. Imaging and isotope tracing showed that classical glucose-consuming organs, muscle, liver, heart, and brain, accounted for only a minority of increased glucose disposal, suggesting RBCs were acting as a significant glucose sink independent of insulin signalling.
The researchers also identified a molecular pathway through which low oxygen redirects glucose metabolism within RBCs, increasing both glucose consumption and oxygen delivery to tissues.
In mouse models of type 1 and type 2 diabetes, approaches that mimicked or induced these RBC adaptations appeared to improve glycaemic control. The authors suggest that targeting RBC metabolism could represent a potential avenue for future therapeutic development, though human studies would be needed to explore clinical relevance.
