High Altitude and Diabetes: How Thin Air May Offer Protection
For years, researchers have observed a curious trend: individuals living at high elevations, where oxygen is scarce, tend to develop diabetes less frequently than those at sea level. Now, scientists at Gladstone Institutes believe they’ve uncovered the reason, revealing a surprising role for red blood cells in regulating blood sugar. This discovery not only solves a longstanding physiological puzzle but as well points toward potential novel treatments for diabetes.
The Hidden Role of Red Blood Cells
The research, published in Cell Metabolism on February 19, 2026, demonstrates that red blood cells act as “glucose sponges” in low-oxygen environments. When oxygen levels drop, these cells shift their metabolism to absorb large amounts of glucose from the bloodstream, effectively lowering blood sugar levels. Gladstone Institutes researchers found this adaptation fuels the cells’ ability to efficiently deliver oxygen to tissues, with the added benefit of glucose control.
“Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” says Isha Jain, PhD, a Gladstone Investigator, core investigator at Arc Institute, and professor of biochemistry at UC San Francisco. SciTechDaily “This discovery could open up entirely new ways to think about controlling blood sugar.”
How Does it Work?
The team initially noticed that mice exposed to low oxygen air exhibited dramatically lower blood glucose levels, rapidly clearing sugar from their bloodstream after eating. However, the organs typically responsible for glucose metabolism – muscle, brain, and liver – couldn’t explain this rapid glucose clearance. ScienceDaily Further investigation revealed that red blood cells were the missing “glucose sink,” absorbing and utilizing significant amounts of glucose.
Researchers, including Angelo D’Alessandro, PhD, of the University of Colorado Anschutz Medical Campus, and Allan Doctor, MD, from University of Maryland, discovered that when oxygen is limited, red blood cells use glucose to generate a molecule that helps release oxygen to tissues. This process is particularly crucial when oxygen is scarce. “What surprised me most was the magnitude of the effect,” says D’Alessandro. “Red blood cells are usually thought of as passive oxygen carriers. Yet, we found that they can account for a substantial fraction of whole-body glucose consumption, especially under hypoxia.”
Potential for New Diabetes Treatments
The benefits of prolonged hypoxia appeared to last for weeks to months after mice were returned to normal oxygen levels. Building on this finding, Jain’s lab developed HypoxyStat, a drug that mimics low oxygen exposure by causing hemoglobin in red blood cells to bind oxygen more tightly, limiting oxygen delivery to tissues.
In mouse models of diabetes, HypoxyStat completely reversed high blood sugar and outperformed existing treatments. “This is one of the first uses of HypoxyStat beyond mitochondrial disease,” Jain explains. “It opens the door to thinking about diabetes treatment in a fundamentally different way – by recruiting red blood cells as glucose sinks.”
Beyond Diabetes: Implications for Other Conditions
The implications of this research extend beyond diabetes. D’Alessandro suggests potential relevance for exercise physiology and for managing pathological hypoxia following traumatic injuries. Changes in red blood cell production and metabolism could impact glucose availability and muscle performance in these scenarios.
“This is just the beginning,” Jain concludes. “There’s still so much to learn about how the whole body adapts to changes in oxygen, and how we could leverage these mechanisms to treat a range of conditions.”
Study Funding
The study was funded by the National Institutes of Health (DP5 DP5OD026398, R01 HL161071, R01 HL173540, R01HL146442, R01HL149714, DP5OD026398), the California Institute for Regenerative Medicine, Dave Wentz, the Hillblom Foundation, and the W.M. Keck Foundation.