For decades scientists have noticed that people who live at high altitudes — where oxygen levels are much lower than at sea level — tend to have lower rates of diabetes, but the biological reason for this has been unclear. Recently, researchers at the Gladstone Institutes have solved this mystery by discovering that red blood cells themselves play a surprising role in lowering blood sugar when oxygen is scarce. Their new study, published in Cell Metabolism, reveals how these abundant cells can shift their metabolism under low-oxygen conditions to absorb glucose from the bloodstream much more actively than previously recognized.
Under normal conditions, red blood cells are primarily thought of as simple oxygen carriers. However, the research team found that in hypoxic environments — like those at high elevation — these cells take on an additional role as major consumers of glucose. Experiments in mice showed that when oxygen levels dropped, not only did the animals produce more red blood cells, but each cell also absorbed significantly more sugar than under normal conditions. This robust uptake explains why the mice exhibited dramatically lower blood glucose levels, a pattern associated with reduced diabetes risk.
When the investigators traced the fate of glucose in hypoxic animals, they were surprised to find that common organs such as liver, muscle, and brain could not account for the disappeared sugar. Instead, advanced imaging techniques revealed that red blood cells were acting as a “glucose sink,” drawing large amounts of sugar out of circulation.
Further analysis showed that red blood cells use the absorbed glucose to make molecules that help them release oxygen to tissues more effectively — a critical adaptation when oxygen is limited. Collaborators on the study included experts from University of Colorado and University of Maryland, emphasizing that this metabolic role of red blood cells was much larger than previously thought.
In addition to explaining altitude-related protection from diabetes, the team also tested a drug called HypoxyStat, which mimics low-oxygen effects without actual hypoxia. In mouse models of diabetes, this compound effectively reversed high blood sugar levels, suggesting new therapeutic avenues for metabolic disease.
Overall, the study highlights an unexpected function of red blood cells and opens the door to novel strategies for controlling blood glucose and treating diabetes.
