Daijiworld Media Network - San Francisco

San Francisco, Feb 23: Living at high altitudes, where oxygen levels are low, may protect against diabetes, and scientists have now identified the biological mechanism behind this long-observed trend.

Researchers at the Gladstone Institutes have discovered that under low-oxygen conditions, red blood cells switch to a new metabolic mode and begin absorbing large amounts of glucose from the bloodstream. The findings, published in Cell Metabolism, suggest that red blood cells act as powerful “glucose sinks,” helping lower blood sugar levels while improving oxygen delivery to tissues.

For years, studies showed that people living at higher elevations develop diabetes less frequently than those at sea level, but the biological explanation remained unclear.

Senior author Isha Jain, a Gladstone Investigator and professor of biochemistry at the University of California, San Francisco, said the research resolves a longstanding question in physiology. She noted that red blood cells represent a previously unrecognised compartment of glucose metabolism, opening new possibilities for blood sugar control.

In earlier experiments, Jain’s team observed that mice exposed to low-oxygen air had significantly lower blood glucose levels. After feeding, sugar disappeared rapidly from their bloodstream. However, traditional glucose-consuming organs such as the liver, muscle and brain did not account for the sudden drop.

Using advanced imaging techniques, the researchers found that red blood cells were responsible for absorbing the excess glucose. Under hypoxic conditions, mice produced more red blood cells, and each cell consumed more glucose than those formed in normal oxygen environments.

To understand the molecular process, the team collaborated with Angelo D'Alessandro of the University of Colorado Anschutz Medical Campus and Allan Doctor from the University of Maryland. Their research showed that in low oxygen settings, red blood cells use glucose to generate molecules that enhance oxygen release to tissues, a critical adaptation in thin air.

The scientists also tested a pill called HypoxyStat, developed in Jain’s laboratory, which mimics low-oxygen exposure by altering how haemoglobin binds oxygen. In diabetic mouse models, the drug reversed high blood sugar levels and performed better than existing treatments.

The study suggests that harnessing red blood cells as glucose sinks could offer a fundamentally new approach to diabetes therapy. Researchers believe the findings may also have broader implications for exercise physiology and trauma care, where oxygen deprivation significantly affects metabolism.

Scientists say further research is needed, but the discovery marks a significant step in understanding how oxygen levels influence whole-body glucose regulation.