Scientists at the Gladstone Institutes have discovered that red blood cells absorb glucose from the bloodstream in low-oxygen environments, offering a potential explanation for why people living at high altitudes have lower rates of diabetes. The findings, published February 19, 2026, in the journal Cell Metabolism, identify a previously unknown metabolic function of red blood cells and suggest a novel approach to diabetes treatment.
For years, researchers have observed a correlation between high-altitude living and reduced diabetes incidence, but the underlying biological mechanism remained elusive. The Gladstone team’s research demonstrates that when oxygen levels drop, red blood cells undergo a metabolic shift, actively taking in glucose. This process effectively turns the cells into “sugar sponges,” lowering blood sugar levels and improving glucose tolerance.
“Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” said Isha Jain, PhD, a Gladstone Investigator, core investigator at Arc Institute, and professor of biochemistry at UC San Francisco. “This discovery could open up entirely new ways to think about controlling blood sugar.”
The research began with observations that mice exposed to low oxygen levels exhibited significantly lower blood glucose levels. Researchers initially sought to identify the organs responsible for this rapid glucose clearance, examining muscle, brain, and liver, but found no significant changes in glucose uptake in those tissues. Further investigation, utilizing specialized imaging techniques, revealed that red blood cells were the primary site of glucose absorption.
“When we gave sugar to the mice in hypoxia, it disappeared from their bloodstream almost instantly,” explained Yolanda Martí-Mateos, PhD, a postdoctoral scholar in Jain’s lab and first author of the study. “We looked at muscle, brain, liver — all the usual suspects — but nothing in these organs could explain what was happening.”
The team collaborated with researchers at the University of Colorado Anschutz Medical Campus and the University of Maryland to understand the molecular mechanisms driving this phenomenon. They found that in low-oxygen conditions, red blood cells utilize glucose to produce a molecule that enhances oxygen release to tissues. This process is particularly crucial when oxygen is scarce.
“What surprised me most was the magnitude of the effect,” said Angelo D’Alessandro, PhD, of the University of Colorado Anschutz Medical Campus. “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.”
The metabolic benefits of prolonged hypoxia were observed to persist for weeks to months after mice were returned to normal oxygen levels. Building on these findings, the researchers tested HypoxyStat, a drug developed in Jain’s lab that mimics the effects of low oxygen exposure. HypoxyStat works by increasing the affinity of hemoglobin in red blood cells for oxygen, limiting its release to tissues. In mouse models of diabetes, HypoxyStat completely reversed high blood sugar and demonstrated superior performance compared to existing treatments.
“What we have is one of the first uses of HypoxyStat beyond mitochondrial disease,” Jain stated. “It opens the door to thinking about diabetes treatment in a fundamentally different way — by recruiting red blood cells as glucose sinks.”
Researchers also suggest potential implications beyond diabetes, including applications in exercise physiology and the treatment of traumatic injuries where hypoxia is a factor. Further research is planned to explore these possibilities.
The study was funded by the National Institutes of Health, the California Institute for Regenerative Medicine, Dave Wentz, the Hillblom Foundation, and the W.M. Keck Foundation.